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Here is a chemical reaction formula: Reactants are aryl halide:C1COCCN1C2=CC(=O)N3C=CC=C(C3=N2)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.00011200000153621659 MOLE;amine:CNC(=O)CN1CCOCC1, amount is: 0.00022400000307243317 MOLE,Reagents are Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+], amount is: 1.1199999789823778e-05 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.1199999789823778e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.1199999789823778e-05 MOLE.Products are 0:CN(C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CN5C4=NC(=CC5=O)N6CCOCC6)C(=O)CN7CCOCC7, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a microwave vial, under nitrogen, at room temperature, a solution of 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (63 mg, 0.11 mmol) in dry toluene (1 mL) was added to a stirred mixture of N-methyl-2-morpholinoacetamide (35.5 mg, 0.22 mmol), Tripotassium phosphate (47.6 mg, 0.22 mmol), rac BINAP (6.99 mg, 0.01 mmol) and Palladium(II) acetate (2.52 mg, 0.01 mmol) in . The resulting mixture was heated in a Biotage Optimiser Microwave reactor under nitrogen at 100 °C for 3 hours. UPLC of the reaction showed no indication of the desired compound - not isolated - reaction abandonned. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=CC(=NC2=C1CN(CC(O2)C3=NC(=CS3)C)C)Cl, amount is: 0.0005970000056549907 MOLE;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, amount is: 0.0005970000056549907 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0009549999958835542 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.990000029967632e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 1.4899999769113492e-05 MOLE.Products are 0:CC1=CC(=NC2=C1CN(CC(O2)C3=NC(=CS3)C)C)NC4=NC(=C(C=C4)C5=CN(N=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-chloro-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (185 mg, 0.60 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (122 mg, 0.60 mmol), Pd2dba3 (13.67 mg, 0.01 mmol), BINAP (18.59 mg, 0.03 mmol) and SODIUM TERT-BUTOXIDE (92 mg, 0.96 mmol) were weighed into a microwave vial. toluene (5 mL) was added and the vial was capped and flushed with argon. The mixture was heated to 100°C in a microwave apparatus for 2 h. The reaction mixture was diluted with dichloromethane and filtered. The solvents were evaporated and the residue was purified by column chromatography on Silica using a gradient of increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give 163 mg og the title product . The enantiomers were separated by HPLC using a chiral stationary phase to give enantiomer 1 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (66.3 mg, 23.25 %) and enantiomer 2 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (65.2 mg, 22.86 %). |
Here is a chemical reaction formula: Reactants are aryl halide:CC(=O)NC1=CN=C(C=N1)Br, amount is: 0.004629999864846468 MOLE;amine:CN1CCNCC1, amount is: 0.023099999874830246 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.009259999729692936 MOLE,Solvents are Solvent:CN(C)C=O, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 0.009259999729692936 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 9.259999933419749e-05 MOLE.Products are 0:CC(=O)NC1=CN=C(C=N1)N2CCN(CC2)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 1-methylpiperazine (2.318 g, 23.14 mmol), N-(5-bromopyrazin-2-yl)acetamide (1 g, 4.63 mmol), tri-tert-butylphosphine (1.873 g, 9.26 mmol), tris(dibenzylideneacetone)dipalladium (0.085 g, 0.09 mmol) and potassium 2-methylpropan-2-olate (1.039 g, 9.26 mmol) were suspended in DMF (9.26 ml) and sealed into a microwave tube. The reaction was heated to 120 °C for 40 minutes in the microwave reactor and cooled to RT. The mixture was diluted with methanol and acidified with HCl, then the solution was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford N-(5-(4-methylpiperazin-1-yl)pyrazin-2-yl)acetamide (0.866 g, 80 %) as a dark oil. Used without further purification. |
Here is a chemical reaction formula: Reactants are amine:C1=CC(=CN=C1)N, amount is: 0.0010100000072270632 MOLE;aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.0010100000072270632 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00203000009059906 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00012199999764561653 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00010099999781232327 MOLE.Products are 0:C1=CC(=CN=C1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: pyridin-3-amine (95 mg, 1.01 mmol), 2,4-dichloropyridine (0.151 mL, 1.01 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (70.4 mg, 0.12 mmol) and cesium carbonate (660 mg, 2.03 mmol) were stirred in dioxane (5 mL). The mixture was purged with nitrogen for 10 minutes. Palladium(II) acetate (22.76 mg, 0.10 mmol) was added and the mixture heated at 100 °C for 2h. The mixture was cooled, filtered and concentrated. The crude product was purified by flash silica chromatography, eluting gradient 5-45% EtOAc in isohexane. Fractions were evaporated to dryness and purified by flash silica chromatography, eluting at 35% EtOAc in isohexane to afford 4-chloro-N-(pyridin-3-yl)pyridin-2-amine (107 mg, 51.5 %) as a cream powder. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=CC(=NC2=C1CN(CC(O2)C3CCCO3)C)Cl, amount is: 0.0010000000474974513 MOLE;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, amount is: 0.0010000000474974513 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0020099999383091927 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 5.020000025979243e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.5100000129896216e-05 MOLE.Products are 0:CC1=CC(=NC2=C1CN(CC(O2)C3CCCO3)C)NC4=NC(=C(C=C4)C5=CN(N=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (205 mg, 1.00 mmol), Pd2(dba)3 (22.99 mg, 0.03 mmol), BINAP (31.3 mg, 0.05 mmol) and SODIUM TERT- BUTOXIDE (193 mg, 2.01 mmol) were placed in a round bottomed flask. The flask was stoppered with a septum and flushed with argon. To this was added a solution of 8-chloro-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (284 mg, 1.00 mmol) in toluene (5 mL) and the resulting mixture was heated to 100°C for 5 h. The reaction mixture was diluted with dichloromethane and filtered, and the solvent was evaporated. The residue was purified by column chromatography on Silica using gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give a mixture of the two diastereoisomers. The major isomer was precipitated from methanol once and from ethanol twice to give 45 mg of Isomer 1 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (45 mg, 10 %) as a single diastereoisomer of unknown stereochemistry. The rest of the material was purified by HPLC to give Isomer 1 (115.7 mg, 25.6 %) and Isomer 2 (39 mg, 8.6 %) of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine. |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC(=O)C2=C(O1)C(=CC(=C2)OC)Br, amount is: 0.00610999995842576 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.006730000022798777 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.008559999987483025 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0007340000011026859 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0003060000017285347 MOLE.Products are 0:CCOC(=O)C1=CC(=O)C2=C(O1)C(=CC(=C2)OC)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium(0) (0.280 g, 0.31 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.457 g, 0.73 mmol), ethyl 8-bromo-6-methoxy-4-oxo-4H-chromene-2-carboxylate (2 g, 6.11 mmol), 1-benzylpiperazine (1.169 mL, 6.73 mmol) and cesium carbonate (2.79 g, 8.56 mmol) were heated under argon to 80 °C in toluene (60 mL) overnight. The reaction mixture was allowed to cool. Ethylacetate was added and the organic mixture was filtered. The filtrate was evaporated onto Silica gel. The crude product was added to a silica gel column and was eluted with MeOH/DCM 0-5%. 1H NMR in CDCl3 is consistent with desired product MS (m+1) = 423. HPLC Peak RT = 3.38 minutes is product. Purity = 63%. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=CC(=CC(=C1NC(=O)CC(C)(C)C)C)Br, amount is: 0.0006709999870508909 MOLE;amine:C1COCCN1, amount is: 0.000805000017862767 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0009399999980814755 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 6.859999848529696e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.389999983482994e-05 MOLE.Products are 0:CC1=CC(=CC(=C1NC(=O)CC(C)(C)C)C)N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Exemplar cmpd from , though employing slightly different Buchwald-Hartwig coupling conditions. Tris(dibenzylidenacetone)dipalladium(0) (31 mg, 0.03 mmol) and 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (27 mg, 0.07 mmol) were stirred in anhydrous toluene (3 mL) for 15 minutes under an argon (g) sparge. To the stirring soluntion was added the N-(4-bromo-2,6-dimethylphenyl)-3,3-dimethylbutanamide (200 mg, 0.67 mmol) and morpholine (0.070 mL, 0.80 mmol) neat, followed by the potassium tert-butoxide (1M in THF) (0.94 mL, 0.94 mmol) via syringe. The mixture was then heated in a sealed vessel to 80 °C for 18hrs before cooling to ambint temperature. The mixture was filtered thru a 0.7uM GMF. The resultant crude solution was subject to flash chromatorgraphy (SiO2 \- 12 g; gradient elution: 100% hexanes for 1 minute then 0% - 80% EtOAc/Hexane over 13 minutes at 30 mL/min) via detection with UV light at 254nm. The appropriate fractions were then stirred over decolorizing carbon (Norit neutral), filtered thru Celite and concentrated to afford the N-(2,6-dimethyl-4-morpholinophenyl)-3,3-dimethylbutanamide (130 mg, 63.7 %) as a off-white solid that appears to be ~90% purity by 1H NMR (CDCl3), though TLC and LCMS reveal one peak. The resultant solid was subject to flash chromatorgraphy (basic alumina - 24 g; gradient elution: 5% EtOAc/Hexane for 1.5 minutes then 5% - 100% EtOAc/Hexane over 11 minutes at 30 mL/min) via detection with UV light at 254nm to afford the N-(2,6-dimethyl-4-morpholinophenyl)-3,3-dimethylbutanamide (130 mg, 63.7 %) again what appears to be ~90% purity by 1H NMR (CDCl3), though TLC and LCMS reveal one peak. Aliqout was provided to for SFC analysis wherein all conditions examined reveal only one peak (attached). 1H NMR analysis in DMSO reveals one clean cmpd. Forming rotamers in CDCl3 with difference exagerated in the morpholino -CH2-N-CH2- protons. |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.0008040000102482736 MOLE;aryl halide:CC1=CC(=CC(=C1NC(=O)CC2CCCC2)C)Br, amount is: 0.0006699999794363976 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0009399999980814755 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 6.859999848529696e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.389999983482994e-05 MOLE.Products are 0:CC1=CC(=CC(=C1NC(=O)CC2CCCC2)C)N3CCOCC3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Exemplar cmpd from, though employing slightly different Buchwald-Hartwig coupling conditions. Tris(dibenzylidenacetone)dipalladium(0) (31 mg, 0.03 mmol) and 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (27 mg, 0.07 mmol) were stirred in anhydrous toluene (3 mL) for 15 minutes under an argon (g) sparge. To the stirring soluntion was added the N-(4-bromo-2,6-dimethylphenyl)-2-cyclopentylacetamide (208 mg, 0.67 mmol) and morpholine (0.070 mL, 0.80 mmol) neat, followed by the potassium tert-butoxide (1M in THF) (0.94 mL, 0.94 mmol) via syringe. he mixture was then heated in a sealed vessel to 80 °C for 18hrs before cooling to ambint temperature. The mixture was filtered thru a 0.7uM GMF. The resultant crude solution was subject to flash chromatorgraphy (SiO2 \- 12 g; gradient elution: 100% hexanes for 1 minute then 0% - 85% EtOAc/Hexane over 14 minutes at 30 mL/min) via detection with UV light at 254nm. The appropriate fractions were then stirred over decolorizing carbon (Norit neutral), filtered thru Celite and concentrated to afford the 2-cyclopentyl-N-(2,6-dimethyl-4-morpholinophenyl)acetamide (47.0 mg, 22.17 %) as a white solid in 90% purity by 1H NMR (CDCl3), though TLC and LCMS reveal one peak. The resultant solid was subject to flash chromatorgraphy (basic alumina - 24 g; gradient elution: 5% EtOAc/Hexane for 1.5 minutes then 5% - 100% EtOAc/Hexane over 11 minutes at 30 mL/min) via detection with UV light at 254nm to afford 2-cyclopentyl-N-(2,6-dimethyl-4-morpholinophenyl)acetamide (28.0 mg, 13.21 %) again what appears to be ~80% purity by 1H NMR (CDCl3), though TLC and LCMS reveal one peak. Aliqout was provided to for SFC analysis wherein all conditions examined reveal only one peak (attached). 1H NMR analysis in DMSO reveals one cmpd. Forming rotamers in CDCl3 with difference exagerated in the morpholino -CH2-N-CH2- protons. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=C(C=CC(=C1)Br)OCC2=CC=CC=C2, amount is: 0.0034099998883903027 MOLE;amine:C[C@@H]1CNCCN1C(=O)OC(C)(C)C, amount is: 0.0035800000187009573 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.004780000075697899 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00013600000238511711 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00010199999815085903 MOLE.Products are 0:C[C@@H]1CN(CCN1)C2=CC(=C(C=C2)OCC3=CC=CC=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To (R)-tert-butyl 2-methylpiperazine-1-carboxylate (0.717 g, 3.58 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.094 g, 0.10 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.085 g, 0.14 mmol) and Sodium tert-butoxide (0.459 g, 4.78 mmol) was added a solution of 1-(benzyloxy)-4-bromo-2-methoxybenzene (1 g, 3.41 mmol) in Toluene (25 mL). The reaction was heated to 80 °C for 18 hours. the reaction was allowed to cool to room temperature and diluted with dcm (50 ml). This was washed with water (2 x 50 ml), dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The crude product was dissolved in hydrochloric acid solution in methanol (4N, 20 ml) and stirred at room temprature overnight. The solvent was removed under reduced pressure.The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford (R)-1-(4-(benzyloxy)-3-methoxyphenyl)-3-methylpiperazine (0.429 g, 40.3 %) as a yellow gum. |
Here is a chemical reaction formula: Reactants are amine:CCONC(=O)C1=CC=CC=C1N, amount is: 0.0006670000148005784 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0003929999948013574 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.930000093532726e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 3.930000093532726e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9600000086938962e-05 MOLE.Products are 0:CCONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)NC3=CC(=NN3C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (22.71 mg, 0.04 mmol), diacetoxypalladium (4.41 mg, 0.02 mmol), 2-amino-N-ethoxybenzamide (120 mg, 0.67 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) and cesium carbonate (256 mg, 0.79 mmol) were weighed out in a µwave vial, sealed and dioxane (4 mL) was added. Reaction was degassed with nitrogen. The reaction was stirred at 90 °C for 12 hours => _incomplete (~90% conversion)_. A few Pd(OAc)2, Xantphos and Cs2CO3 were added. Reaction was degassed with nitrogen and stirred at 90°C for 2 hours => _complete._ The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane and MeOH and silica (40-63 µm) was added. Mixture was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane. Solvent was evaporated to afford product as a pale yellow foam. This was dissolved in Et2O, petroleum ether was added and the resulting precipitate was sonicated for 10 minutes. Solid was filtered and dried under high vacuum to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-ethoxybenzamide (127 mg, 74.5 %) as a white solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0003929999948013574 MOLE;amine:C1=CC=C(C(=C1)C(=O)NOCCO)N, amount is: 0.0006670000148005784 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.930000093532726e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 3.930000093532726e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9600000086938962e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOCCO)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (22.71 mg, 0.04 mmol), diacetoxypalladium (4.41 mg, 0.02 mmol), 2-amino-N-(2-hydroxyethoxy)benzamide (131 mg, 0.67 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) and cesium carbonate (256 mg, 0.79 mmol) were weighed out in a µwave vial, sealed and dioxane (4 mL) was added. Reaction was degassed with nitrogen. The reaction was stirred at 90 °C for 12 hours => _incomplete (~85% conversion)_. A few Pd(OAc)2, Xantphos and Cs2CO3 were added. Reaction was degassed with nitrogen and stirred at 90°C for 2 hours => _almost complete._ The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane and MeOH and silica (40-63 µm) was added. Mixture was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 12% methanol in ethyl acetate. Solvent was evaporated to afford product as a yellow foam. This was triturated in Et2O and petroleum ether and the resulting precipitate was sonicated for 10 minutes. Solid was filtered and dried under high vacuum to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-(2-hydroxyethoxy)benzamide (86 mg, 48.6 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C=N1)C2=CC=C(C=C2)N, amount is: 1.8200000340584666e-05 MOLE;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 1.8200000340584666e-05 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 9.100000170292333e-06 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 1.819999965846364e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.819999965846364e-06 MOLE.Products are 0:CC1=NN(C=N1)C2=CC=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (5.00 mg, 0.02 mmol) and 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (3.17 mg, 0.02 mmol) in DME (.5 mL) was added via a syringe to a capped microwave vial containing PALLADIUM(II) ACETATE (0.409 mg, 1.82 µmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.638 mg, 1.82 µmol), CESIUM CARBONATE (8.89 mg, 0.03 mmol) and KI (1.511 mg, 9.10 µmol) under an argon atmosphere. The resulting mixture was heated to 100°C in a microwavwe apparatus for 1 h and analyzed by LCMS. No product. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 1.8200000340584666e-05 MOLE;amine:CC1=NN(C=N1)C2=CC=C(C=C2)N, amount is: 1.8200000340584666e-05 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 2.7300000510876998e-05 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 1.819999965846364e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.819999965846364e-06 MOLE.Products are 0:CC1=NN(C=N1)C2=CC=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (5.00 mg, 0.02 mmol) and 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (3.17 mg, 0.02 mmol) in DME (.5 mL) was added via a syringe to a capped microwave vial containing PALLADIUM(II) ACETATE (0.409 mg, 1.82 µmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.638 mg, 1.82 µmol) and CESIUM CARBONATE (8.89 mg, 0.03 mmol) under an argon atmosphere. The resulting mixture was heated to 100°C in a microwave apparatus for 1 h and analyzed by LCMS. No product. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C=N1)C2=CC=C(C=C2)N, amount is: 1.8200000340584666e-05 MOLE;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 1.8200000340584666e-05 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 2.7300000510876998e-05 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 1.819999965846364e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.819999965846364e-06 MOLE.Products are 0:CC1=NN(C=N1)C2=CC=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (5.00 mg, 0.02 mmol) and 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (3.17 mg, 0.02 mmol) in DME (0.5 mL) was added via a syringe to a capped microwave vial containing PALLADIUM(II) ACETATE (0.409 mg, 1.82 µmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.638 mg, 1.82 µmol) and KOtBu (3.06 mg, 0.03 mmol) under an argon atmosphere. The resulting mixture was heated to 100°C in a microwavwe apparatus for 1 h and analyzed by LCMS. No product. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C=N1)C2=CC=C(C=C2)N, amount is: 1.8200000340584666e-05 MOLE;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 1.8200000340584666e-05 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 2.7300000510876998e-05 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.819999965846364e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.819999965846364e-06 MOLE.Products are 0:CC1=NN(C=N1)C2=CC=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (5.00 mg, 0.02 mmol) and 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (3.17 mg, 0.02 mmol) in DME (.5 mL) was added via a syringe to a capped microwave vial containing PALLADIUM(II) ACETATE (0.409 mg, 1.82 µmol), XANTPHOS (1.053 mg, 1.82 µmol) and CESIUM CARBONATE (8.89 mg, 0.03 mmol) under an argon atmosphere. The resulting mixture was heated to 100°C in a microwavwe apparatus for 1 h and analyzed by LCMS. No product. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C=N1)C2=CC=C(C=C2)N, amount is: 1.8200000340584666e-05 MOLE;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 1.8200000340584666e-05 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 2.7300000510876998e-05 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 1.819999965846364e-06 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 9.09999982923182e-07 MOLE.Products are 0:CC1=NN(C=N1)C2=CC=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (5.00 mg, 0.02 mmol) and 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (3.17 mg, 0.02 mmol) in DME (.5 mL) was added via a syringe to a capped microwave vial containing Pd2(dba)3 (0.833 mg, 0.91 µmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.638 mg, 1.82 µmol) and Cs2CO3 (8.89 mg, 0.03 mmol) under an argon atmosphere. The resulting mixture was heated to 100°C in a microwavwe apparatus for 1 h and analyzed by LCMS. No product. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=C(C=C(O2)C(=O)N)C(=C1)Br, amount is: 0.0024999999441206455 MOLE;amine:C1CNCCN1, amount is: 0.012500000186264515 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.004999999888241291 MOLE,Solvents are Solvent:C1CCOC1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0002500000118743628 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0001250000059371814 MOLE.Products are 0:C1CN(CCN1)C2=C3C=C(OC3=CC=C2)C(=O)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The crude product from EN03731-54-001, 4-bromobenzofuran-2-carboxamide (0.600 g, 2.5 mmol), was dissolved in THF (18 mL) and water (18.00 mL). To this mixture were added piperazine (1.077 g, 12.50 mmol), Cesium carbonate (1.629 g, 5.00 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.114 g, 0.13 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.156 g, 0.25 mmol) and the reaction was heated at 70 °C over night. 2010-04-13 No product was detected. The reaction mixture was filtered and solvents were removed in vacuo. The residue was partitioned between methylene chloride and water. The organic layer was washed with 1M HCl(aq), dired with sodium sulfate, filtered, concentrated and purified by flash chromatography(Isolute Si 70g, methylene chloride: methanol; 97:3). No product could be detected/isolated. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)N1CCNCC1, amount is: 0.0009260000078938901 MOLE;aryl halide:CC1=C(C(=CC=C1)Br)[N+](=O)[O-], amount is: 0.0009260000078938901 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00203999993391335 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0001849999971454963 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.259999933419749e-05 MOLE.Products are 0:CC1=C(C(=CC=C1)N2CCN(CC2)C(=O)OC(C)(C)C)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl piperazine-1-carboxylate (172 mg, 0.93 mmol) and 1-bromo-3-methyl-2-nitrobenzene (0.124 mL, 0.93 mmol), were added to a stirred solution of diacetoxypalladium (20.78 mg, 0.09 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (107 mg, 0.19 mmol) and cesium carbonate (664 mg, 2.04 mmol) dissolved in dioxane (3 mL). The resulting solution was stirred at 80 °C under nitrogen overnight. The reaction mixture was filtered, dried under vaccum. The crude product was purified by flash chromatography on silica gel eluting with 5 to 15% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-(3-methyl-2-nitrophenyl)piperazine-1-carboxylate (50.0 mg, 16.81 %) as a orange oil. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=C(C=C1Br)F)C=O, amount is: 0.0032999999821186066 MOLE;amine:CC(C)(C)OC(=O)N, amount is: 0.00395999988541007 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.004689999856054783 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0002640000020619482 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 0.0001320000010309741 MOLE.Products are 0:CC(C)(C)OC(=O)NC1=CC(=C(C=C1)C=O)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of 4-bromo-2-fluorobenzaldehyde (0.670 g, 3.30 mmol) dissolved in toluene (10 mL) was treated with tert-butyl carbamate (0.464 g, 3.96 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.164 g, 0.26 mmol), Bis(dibenzylideneacetone)palladium (0.076 g, 0.13 mmol) and cesium carbonate (1.527 g, 4.69 mmol) under nitrogen. The mixture was degassed under vacuum several times before heating at 100 °C for 24 hours. Reaction incomplete so heated for further 10 hours. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (250 mL X 2). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution 10% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 3-fluoro-4-formylphenylcarbamate (0.660 g, 84 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=C(C=C1Br)F)C=O, amount is: 0.015200000256299973 MOLE;amine:CC(C)(C)OC(=O)N, amount is: 0.018300000578165054 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.02160000056028366 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0012199999764561653 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 0.0006089999806135893 MOLE.Products are 0:CC(C)(C)OC(=O)NC1=CC(=C(C=C1)C=O)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of 4-bromo-2-fluorobenzaldehyde (3.09 g, 15.22 mmol) dissolved in toluene (40 mL) was treated with tert-butyl carbamate (2.140 g, 18.27 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.758 g, 1.22 mmol), Bis(dibenzylideneacetone)palladium (0.350 g, 0.61 mmol) and cesium carbonate (7.04 g, 21.62 mmol) under nitrogen. The mixture was degassed under vacuum several times before heating at 100 °C for 30 hours. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (250 mL X 2). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution 10% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 3-fluoro-4-formylphenylcarbamate (3.55 g, 97 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)I, amount is: 0.0021800000686198473 MOLE;amine:CC(C)(C)OC(=O)NCCC1CCNCC1, amount is: 0.001500000013038516 MOLE,Reagents are Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+], amount is: 0.003000000026077032 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 0.0001500000071246177 MOLE;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Pd], amount is: 0.0001500000071246177 MOLE.Products are 0:CC(C)(C)OC(=O)NCCC1CCN(CC1)C2=CC=CC=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of tert-butyl 2-(piperidin-4-yl)ethylcarbamate (0.342 g, 1.5 mmol) in anhydrous DME were added iodobenzene (0.444 g, 2.18 mmol), bis(tri-t- butylphosphine)palladium(0) (0.077 g, 0.15 mmol) and potassium phosphate (0.245 mL, 3.00 mmol). The reaction was heated to 100°C overnight. This reaction did not work. |
Here is a chemical reaction formula: Reactants are aryl halide:CN(C)C(=O)C1=CC2=C(O1)C(=CC=C2)Br, amount is: 0.0048500001430511475 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.006300000008195639 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0067900000140070915 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.00048499999684281647 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00024199999461416155 MOLE.Products are 0:CN(C)C(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The mixture of Tris(dibenzylideneacetone)dipalladium(0) (0.222 g, 0.24 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.231 g, 0.48 mmol) in dioxane (10 mL) (degassed with argon for 5 min) was heated at 95 °C under argon for 5 min . This was transferred to a flask containing 7-bromo-N,N-dimethylbenzofuran-2-carboxamide (1.3 g, 4.85 mmol), 1-benzylpiperazine (1.111 g, 6.30 mmol) and Cesium carbonate (2.212 g, 6.79 mmol) in dioxane (10 mL) (degassed with argon for 5 min). The resulting mixture was heated at 95 °C over night. After cooling, the reaction mixture was filtered, the solid washed with DCM and concentrated. The product was purified by isco (DCM:MeOH; 0-3%). A small portion was also purified by prepLC giving EN02745-79-002. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)Br, amount is: 0.0009549999958835542 MOLE;amine:CC(C)(C)OC(=O)NCCC1CCNCC1, amount is: 0.001500000013038516 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.00019099999917671084 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00019099999917671084 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.549999958835542e-05 MOLE.Products are 0:CC(C)(C)OC(=O)NCCC1CCN(CC1)C2=CC=CC=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: palladium(II) acetate (21.45 mg, 0.10 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (111 mg, 0.19 mmol) were placed in a round-bottomed vessel that was filled with nitrogen. Toluene (0.8 mL) was added and the mixture was heated to 50°C for 30 min. sodium tert-butoxide (138 mg, 1.43 mmol) was added to a second vessel and inerted with nitrogen. tert-butyl 2-(piperidin-4-yl)ethylcarbamate (342 mg, 1.5 mmol) and bromobenzene (150mg, 0.96 mmol) and toluene (1.4 mL) were added. 14/04 2009 13:57:24 +0200 The catalyst solution was added to the reagent mixture and the combined mixture was heated to reflux for several hours. The reaction did not work. |
Here is a chemical reaction formula: Reactants are amine:C1CN(CCN1)CCC2=CC=CC=C2, amount is: 0.00025400001322850585 MOLE;aryl halide:C1=CC2=C(C(=C1)Br)OC=C2, amount is: 0.00025400001322850585 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0003549999964889139 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.0200000360782724e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 5.079999937152024e-06 MOLE.Products are 0:C1CN(CCN1CCC2=CC=CC=C2)C3=CC=CC4=C3OC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A dried Radley tube was charged with rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (6.32 mg, 10.15 µmol), Tris(dibenzylideneacetone)dipalladium(0) (4.65 mg, 5.08 µmol) and Sodium tert- butoxide (34.1 mg, 0.36 mmol). Argon atmosphere was introduced and toluene (3ml) was added followed by 7-bromobenzofuran (50mg, 0.25 mmol) and 1-phenethylpiperazine (48.3 mg, 0.25 mmol). The reaction mixture was heated at reflux over night. 2010-03-25 The reaction mixture was filtered, concentrated and purified by flash chromatography (Isolute Si 10g, heptane: ethyl acetate; 4:1) to give 1-(benzofuran-7-yl)-4-phenethylpiperazine (48.3 mg, 62.1 %) |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], amount is: 0.0006459999713115394 MOLE;amine:C[C@@H]1CNC[C@@H](N1)C, amount is: 0.0019399999873712659 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009699999936856329 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 9.049999789567664e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.459999713115394e-05 MOLE.Products are 0:C[C@@H]1CN(C[C@@H](N1)C)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 4-bromo-1-methoxy-2-nitrobenzene (150 mg, 0.65 mmol) in dioxane (4 mL) was added (2R,6S)-2,6-dimethylpiperazine (221 mg, 1.94 mmol) followed by cesium carbonate (316 mg, 0.97 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (56.4 mg, 0.09 mmol) and diacetoxypalladium (14.51 mg, 0.06 mmol). The resulting mixture was heated at 100 °C under argon over night (black). LCMS Ok. The solids were filtered through celite and washed with ethyl acetate. The ethyl acetate was evaporated under reduced pressure and the crude product was purified by flash- chromatograpy eluated with dichloromethane/ Methanol + 0.2% Et3N 100/0 =>90/10 over 20 min. The pure fractions was collected and concentrated to give (3R,5S)-1-(4-methoxy-3-nitrophenyl)-3,5-dimethylpiperazine (96 mg, 56.0 %) as red solid. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], amount is: 0.006459999829530716 MOLE;amine:C[C@@H]1CNC[C@@H](N1)C, amount is: 0.01940000057220459 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.009700000286102295 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0009050000226125121 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0006459999713115394 MOLE.Products are 0:C[C@@H]1CN(C[C@@H](N1)C)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a solution of 4-bromo-1-methoxy-2-nitrobenzene (1500 mg, 6.46 mmol) in dioxane (40 mL) was added (2R,6S)-2,6-dimethylpiperazine (2215 mg, 19.39 mmol) followed by cesium carbonate (3159 mg, 9.70 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (564 mg, 0.91 mmol) and diacetoxypalladium (145 mg, 0.65 mmol). The resulting mixture was heated at 100 °C under argon over night (black). LCMS Ok. The solids were filtered through celite and washed with ethyl acetate. The ethyl acetate was evaporated under reduced pressure and the crude product was purified by flash- chromatograpy eluated with Dichloromethane/ 2 M NH3 in Methanol 100/0 =>80/20 over 20 min. The pure fractions was collected and concentrated to give (3R,5S)-1-(4-methoxy-3-nitrophenyl)-3,5-dimethylpiperazine (1540 mg, 90 %) as red solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CNC(=O)C1=C(C=CC=C1OC)NC2=CC(=NC=C2C(F)(F)F)Cl, amount is: 0.004610000178217888 MOLE;amine:CC1=NN(C(=C1)N)C, amount is: 0.00471000000834465 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.005539999809116125 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0007379999733529985 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00036899998667649925 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (1.66 g, 4.61 mmol)_ _,_ _1,3-dimethyl-1H-pyrazol-5-amine (0.523 g, 4.71 mmol)_ _,_ _diacetoxypalladium (0.083 g, 0.37 mmol)_ _,_ _(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.427 g, 0.74 mmol)_ _and_ _cesium carbonate (1.804 g, 5.54 mmol)_ _were mixed together in_ _dioxane (30 mL)_ _. Reaction was degassed with argon and was stirred at_ _90 °C_ _for 3 hours under argon.The mixture was filtered ,the filtrate was concentrated and purified by flash chromatography on silica gel 15-40µm eluting with __0_ _to_ _4_ _% methanol in CH2Cl2/AcOEt (60/40).The product obtained was not enough pure so the product was repurified by flash chromatography on silica gel 15-40µm eluting with 0 to 4% methanol in CH2Cl2/AcOEt (60/40).The solvent was evaporated to dryness to afford _2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy- N-methylbenzamide (0.882 g, 44.0 %) _as a _beige __ solid _._ _EN 02814-27-01_ |
Here is a chemical reaction formula: Reactants are aryl halide:CC(C)OCC1CN(CC2=C(O1)N=C(C=C2)Cl)C, amount is: 0.0005799999926239252 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0005799999926239252 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0017399999778717756 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 5.8000001445179805e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 5.8000001445179805e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)COC(C)C)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-chloro-2-(isopropoxymethyl)-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.157 g, 0.58 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.118 g, 0.58 mmol), Palladium acetate (0.013 g, 0.06 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.020 g, 0.06 mmol) and Cesium carbonate (0.567 g, 1.74 mmol) were placed in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (5 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. Very little product. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. Still have a lot of startingmaterial (oxazepine) left. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and the residue was partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was separated by a Phase Separator and concentrated giving 2-(isopropoxymethyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.013 g, 5.28 %). |
Here is a chemical reaction formula: Reactants are aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.0006549999816343188 MOLE;amine:CC1=NN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0006549999816343188 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.001970000099390745 MOLE,Solvents are Solvent:CCO, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 6.549999670824036e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.549999670824036e-05 MOLE.Products are 0:CC1=NN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (180 mg, 0,66 mmol), 3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (134 mg, 0,66 mmol), Palladium acetate (14,71 mg, 0,07 mmol), 2-(Dicyclohexylphosphino)biphenyl (22,96 mg, 0,07 mmol) and Cesium carbonate (640 mg, 1,97 mmol) were mixed in DME (3 mL) in a microwave vial. EtOH (0,3 mL) was added and the mixture was run for 1 hour at 100°C in a microwave reactor. the reaction had to be run for an additional 2 hours with more catalyst and ligand added. the mixture was filtered and purified using flash chromatography 0-10% MeOH in DCM. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=C(C(=NN1C)C)NC2=NC=C(C(=C2)I)C(F)(F)F, amount is: 0.0019199999514967203 MOLE;amine:CONC(=O)C1=CC=CC=C1N, amount is: 0.0032599999103695154 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0038300000596791506 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00028700000257231295 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0001720000000204891 MOLE.Products are 0:CC1=C(C(=NN1C)C)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)C(F)(F)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-amino-N-methoxybenzamide (541 mg, 3.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (166 mg, 0.29 mmol), cesium carbonate (1249 mg, 3.83 mmol) and diacetoxypalladium (38.7 mg, 0.17 mmol) were added to a stirred solution of 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyridin-2-amine (759 mg, 1.92 mmol) dissolved in dioxane (20 mL) in a µwave vial at RT. Argon was let to bubble in the mixture for 5 minutes and the resulting slurry was then stirred at 90 °C for 15 hours. Lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane, filtered, silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 30 to 100% ethyl acetate in petroleum ether. The solvent was evaporated to dryness, the remainning gum was taken up in DCM and concentrated in the cold. The precipitate was collected by filtration, washed with diethyl ether and dried to a constant weight to afford N-methoxy-2-(5-(trifluoromethyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)benzamide (742 mg, 89 %) (batch EN03692-99-01) as a off-white solid. NMR showed the presence of solvents (ethyl acetate and diethyl ether). The solid was then dried several days under vacuum at 55°C to removed these solvents (--> batch EN03692-99-02 (723 mg, 1.664 mmol, 87 %)) : unsuccessfully! **Analysis: - NMR (CDE) -- > strenght = 95%, ****ethyl acetate** **= 0.06 mole/mole and diethyl ether = 0.11 mole/mole** ** \- analytical lcms (DDO) --> purity = 99%** |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, amount is: 0.009290000423789024 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.010200000368058681 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.01209999993443489 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.0009289999725297093 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00046499999007210135 MOLE.Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 20/10 2009 10:10:14 +0200 To ethyl 4-bromobenzofuran-2-carboxylate (2.50 g, 9.29 mmol) and 1-benzylpiperazine (1.776 mL, 10.22 mmol) in dry degassed dioxane (30 mL) were added Cesium carbonate (3.94 g, 12.08 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.443 g, 0.93 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.425 g, 0.46 mmol) under argon and the reaction heated at 95°C o/n. All starting material consumed. The crude solution was pooled with the corresponding solution in EN03307-46 Water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (MgSO4), filtered and evaporated. The crude was purified by flash chrom. (SiO2; Heptane/EtOAc 70/30) to give 3.05 g (50%) of the product as a yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, amount is: 0.003719999920576811 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.00482999999076128 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.004459999967366457 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C, amount is: 0.0002229999954579398 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 7.429999823216349e-05 MOLE.Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **Purpose:** Buchwald-Hartwig coupling using unpurified ethyl 4-bromobenzofuran-2-carboxylate. The analysis on crude 4-bromobenzofuran-2-carboxylate shows traces of non cyclized and non aromoatized by-products. 2010-03-10 16:38:11: To a 25 mL rounbottomed flask was added ethyl 4-bromobenzofuran-2-carboxylate (1 g; 3.72 mmol) and toluene (10 mL/g-bulk-LR; 10 mL). The mixture was concentrated under reduced pressure to remove traces of water. The procedure was repeated once more. and finally toluene (10 mL/g-bulk-LR; 10 mL). The system was inerted three times and stirred under nitrogen gas. 17:03:56: To the homogenous mixture was added 1-benzylpiperazine (1.3 eq; 0.852 g; 0.84 mL; 4.83 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.02 eq; 68 mg; 0.07 mmol), 2-(DI-T-BUTYLPHOSPHINO)BIPHENYL (0.06 eq; 67 mg; 0.22 mmol) and CESIUM CARBONATE (1.2 eq; 1.453 g; 4.46 mmol). The system was inerted three times and stirred under nitrogen gas. 17:07:37: The Tj was set to Tj=100 °C. The mixture was stirred under nitrogen gas over night. 2010-03-11 08:42:44: IPC1 (15 h) sample was gathered and diluted with methanol. The analysis (EN03690-35-001-A) showed only 16 % conversion. **Results and conclusion:** The experiment was discarded due to poor conversion. |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, amount is: 0.003719999920576811 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.0033400000538676977 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00482999999076128 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.00037200000951997936 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00018600000475998968 MOLE.Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: ethyl 4-bromobenzofuran-2-carboxylate (1 g, 3.72 mmol), 1-Benzylpiperazine (0.580 mL, 3.34 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.170 g, 0.19 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.177 g, 0.37 mmol) and CESIUM CARBONATE (1.574 g, 4.83 mmol) in dioxane (5 mL) were heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate (0.360 g, 26.6 %). MS (m+1) = 365.6. HPLC Peak RT = 3.33 minutes is product. Purity = 96%. |
Here is a chemical reaction formula: Reactants are amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.00482999999076128 MOLE;aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, amount is: 0.003719999920576811 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.005200000014156103 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00014899999951012433 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 7.429999823216349e-05 MOLE.Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **Purpose:** Buchwald-Hartwig coupling using unpurified ethyl 4-bromobenzofuran-2-carboxylate. The analysis on crude 4-bromobenzofuran-2-carboxylate shows traces of non cyclized and non aromoatized by-products. 2010-03-02 15:25:22: To a 25 mL roundbottomed flask was added ethyl 4-bromobenzofuran-2-carboxylate (LR; 1 g; 3.72 mmol) and toluene (7 mL/g-bulk- LR; 7 mL). The mixture was concentrated under reduced pressure. To the mixture was added toluene (7 mL/g-bulk-LR; 7 mL) and the mixture was concentrated a second time under reduced pressure. To the mixture was added toluene (7 mL/g-bulk-LR; 7 mL) followed by 1-benzylpiperazine (1.3 eq; 0.852 g; 0.84 mL), BINAP (0.04 eq; 93 mg) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.02 eq; 68 mg). The mixture was stirred for 5 minutes followed by addition of POTASSIUM TERT-BUTOXIDE (1.4 eq; 0.58 g). The mixture is stirred at Tm=50 °C. 15:45:57: IPC1 (15 min) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-F) which indicated 44 % conversion 17:09:21: IPC2 (100 min) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-H) which indicated 95 % conversion. 17:20:00: The temperature was allowed to reach rt and the mixture was stirred over night. 2010-03-03 09:51:29: IPC3 (18 h) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-J) which indicated +99 % conversion. 10:10:32: The mixture was transfered to a mixture consisting of 700 mM acetate buffer pH=2 (12.5 mL/g-bulk-LR; 12.5 mL) and isopropyl acetate (6.2 mL/g-bulk- LR; 6.2 mL) to give pH=5.65. To the mixture was added 4 M aqueous sulfuric acid (1.77 mL/g-bulk-LR; 1.77 mL) to give pH=2. The mixture was stirred for 15 minutes. The phases were separated and analyzed by means of HPLC-UV 12:32:57: To the water phase was added dichloromethane (10 mL/g-bulk-LR; 10 mL). The mixture was stirred and 50 % aqueous sodium hydroxide (1 mL) was added to give pH=12. The phases were separated and analyzed by means of HPLC- UV. The organic phase was concentrated under reduced pressure to give yellow oil. The crude product was purified by means of column chromatography (40 g SiO2; 4 % MeOH, 1 NH3 in MeOH in DCM; Rf=0.2). Yellow solid was obtained (250 mg). 1H NMR showed not correct product. **Result:** Correct product was not isolated. |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, amount is: 0.01860000006854534 MOLE;amine:C1CN(CCN1)CC2=CC=CC=C2, amount is: 0.01860000006854534 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.02419999986886978 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.0018599999602884054 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0009289999725297093 MOLE.Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)CC4=CC=CC=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: ethyl 4-bromobenzofuran-2-carboxylate (5 g, 18.58 mmol), 1-benzylpiperazine (3.22 mL, 18.58 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso- propyl-1,1'-biphenyl (0.886 g, 1.86 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.851 g, 0.93 mmol) and CESIUM CARBONATE (7.87 g, 24.16 mmol) were heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate (2.160 g, 31.9 %). MS (m+1) = 365.6. HPLC Peak RT = 3.30 minutes is product. Purity = 94%. |
Here is a chemical reaction formula: Reactants are amine:C1CNCCC12OCCO2, amount is: 0.0348999984562397 MOLE;aryl halide:C1=CC=NC(=C1)Br, amount is: 0.0348999984562397 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.052400000393390656 MOLE,this reaction does not need solvents,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.001500000013038516 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.001500000013038516 MOLE.Products are 0:C1CN(CCC12OCCO2)C3=CC=CC=N3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The same procrdure as EN03653-93-01. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(N=C1Cl)Cl, amount is: 0.001339999958872795 MOLE;amine:C1=CC(=CC(=C1)S(=O)(=O)N)N, amount is: 0.001339999958872795 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00267999991774559 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0001610000035725534 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.710000161547214e-05 MOLE.Products are 0:C1=CC(=CC(=C1)S(=O)(=O)N)NC2=NC=CC(=N2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2,4-dichloropyrimidine (200 mg, 1.34 mmol), 3-aminobenzenesulfonamide (231 mg, 1.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (93 mg, 0.16 mmol), cesium carbonate (875 mg, 2.68 mmol) and diacetoxypalladium (15.07 mg, 0.07 mmol) were suspended in dioxane (5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (150 mL) and washed with water (150 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 4% (10:1 MeOH/NH3 (aq)) in DCM. NMR analysis showed a trace amount of product. |
Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC(=CN=C1)Br, amount is: 0.0008689999813213944 MOLE;amine:C1COCCN1, amount is: 0.0009560000034980476 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 4.350000017439015e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 4.350000017439015e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.1699999706470408e-05 MOLE.Products are 0:CCOC(=O)C1=CC(=CN=C1)N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: ethyl 5-bromonicotinate (200 mg, 0.87 mmol), morpholine (0.083 mL, 0.96 mmol), sodium 2-methylpropan-2-olate (167 mg, 1.74 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (17.11 mg, 0.04 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (19.90 mg, 0.02 mmol) were suspended in dioxane (5 mL) and sealed into a microwave tube. The reaction was heated to 100 °C for 1 hour in the microwave reactor and cooled to RT. LCMS analysis appeared to indicate addition of 2 morpholine rings and the reaction was abandoned. |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.0009560000034980476 MOLE;aryl halide:CCOC(=O)C1=CC(=CN=C1)Br, amount is: 0.0008689999813213944 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 4.350000017439015e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 4.350000017439015e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.1699999706470408e-05 MOLE.Products are 0:CCOC(=O)C1=CC(=CN=C1)N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: ethyl 5-bromonicotinate (200 mg, 0.87 mmol), morpholine (0.083 mL, 0.96 mmol), sodium 2-methylpropan-2-olate (167 mg, 1.74 mmol) and 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (17.11 mg, 0.04 mmol) were suspended in dioxane (5 mL). The reaction flask was purged with nitrogen and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (19.90 mg, 0.02 mmol) was added. The reaction was stirred at 80 °C for 90 minutes. LCMS analysis appeared to indicate addition of 2 morpholine rings and the reaction was abandoned. |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.006779999937862158 MOLE;aryl halide:CC(C)(C)OC(=O)C1=CC(=CN=C1)Br, amount is: 0.005419999826699495 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.01080000028014183 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0008140000281855464 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00027099999715574086 MOLE.Products are 0:CC(C)(C)OC(=O)C1=CC(=CN=C1)N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl 5-bromonicotinate (1.4 g, 5.42 mmol), morpholine (0.591 ml, 6.78 mmol), cesium carbonate (3.53 g, 10.85 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.507 g, 0.81 mmol) were dissolved in toluene (20 ml). The reaction flask was purged with nitrogen and diacetoxypalladium (0.061 g, 0.27 mmol) was added. The resulting suspension was stirred at 80 °C for 5 hours. The reaction mixture was diluted with EtOAc (100 mL) and washed with water (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 5-morpholinonicotinate (0.381 g, 26.6 %) as a yellow oil which solidified on standing. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=C(C=C1Br)NN=C2, amount is: 0.015200000256299973 MOLE;amine:C1=CC=C(C(=C1)N)Cl, amount is: 0.016699999570846558 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.030500000342726707 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0022799998987466097 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0015200000489130616 MOLE.Products are 0:C1=CC=C(C(=C1)NC2=CC3=C(C=C2)C=NN3)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.342 g, 1.52 mmol) and rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1.422 g, 2.28 mmol) were added to a stirred slurry of 2-chloroaniline (1.763 mL, 16.75 mmol), 6-bromo-1H-indazole (3 g, 15.23 mmol) and cesium carbonate (9.92 g, 30.45 mmol) in toluene (50 mL) at 23°C under nitrogen. The resulting slurry was stirred at 80 °C for 2 hours. The reaction was incomplete (both SM left) so the temperature was increased to 100°C and the reaction mixture was stirred for a further 2 hours. Mainly 2 SM detected. problem of solubility of bromoindazole? The reaction was incomplete and further Palladium(II) acetate (30mg), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (200mg) and cesium carbonate (1g) were added as well as dioxane and the slurry was stirred at 110 °C for a further 3 hours. Only SMs detected. No further work on this sample. Perform coupling with reverse coupling partners using Boc 6-aminoindazole. Known to work as used in project. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.00021800000104121864 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0002840000088326633 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0006549999816343188 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 2.1800000467919745e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.1800000467919745e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5=CC=CC=C5)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (60.0 mg, 0.22 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (57.7 mg, 0.28 mmol), palladium(II) acetate (4.90 mg, 0.02 mmol), 2-(Dicyclohexylphosphino)biphenyl (7.65 mg, 0.02 mmol) and CS2CO3 (213 mg, 0.66 mmol) were weighed into a microwave vial. The vial was capped and flushed with argon. DME (4 mL) was added and the mixture was heated to 100°C in a microwave apparatus for 1 h. The cooled reaction mixture was diluted with dichloromethane and methanol, filtered through a plug of Celite and the solvents were evaporated. The residue was purified by HPLC to give 36 mg (37 % Yield) of the title product. |
Here is a chemical reaction formula: Reactants are amine:CN1CCNCC1, amount is: 0.020800000056624413 MOLE;aryl halide:C1=CC(=CC=C1O)Br, amount is: 0.01730000041425228 MOLE,Reagents are Base:[Li+].C[Si](C)(C)[N-][Si](C)(C)C, amount is: 0.039900001138448715 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.00034699999378062785 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00017299999308306724 MOLE.Products are 0:CN1CCN(CC1)C2=CC=C(C=C2)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (0.039 g, 0.17 mmol) was added in one portion to 4-bromophenol (3 g, 17.34 mmol) and 1-methylpiperazine (2.308 mL, 20.81 mmol) in toluene (87 mL) at 25°C under nitrogen. To this was added toluene (87 mL) then a solution of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.123 mL, 0.35 mmol) in Toluene (1 mL) and finally 1M LITHIUM BIS(TRIMETHYLSILYL)AMIDE (39.9 mL, 39.88 mmol) in THF was added dropwise over 1 minute. The resulting mixture was stirred at 80 °C for 18 hours. The reaction was allowed to cool to room temperature, SiO2 (23g) was added and evaporated to dryness. The crude product was purified by flash silica chromatography (120g), elution gradient 0 to 10% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford 4-(4-methylpiperazin-1-yl)phenol (1.700 g, 51.0 %) as a beige solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1OC2=C(C(=CN=C2O1)Cl)N, amount is: 0.0763000026345253 MOLE;amine:C1CC1C(=O)NC2=NC=CC(=C2)Cl, amount is: 0.0763000026345253 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.19099999964237213 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.008390000090003014 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.006099999882280827 MOLE.Products are 0:C1CC1C(=O)NC2=NC=CC(=C2)NC3=C4C(=NC=C3Cl)OCO4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution of N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (15 g, 76.28 mmol) in dioxane (200 mL) was added 6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-amine (13.16 g, 76.28 mmol), cesium carbonate (62.1 g, 190.71 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.86 g, 8.39 mmol) and diacetoxypalladium (1.370 g, 6.10 mmol). Mixture was degassed 3 times with N2 and heated at reflux (110°C) for 4h: OK. Reaction was cooled down, diluted with 200mL of CH2Cl2 and filtered. The filtrate was concentrated and the residue purified on silica, eluting with 2% of MeOH in CH2Cl2. Solvent were evaporated, diluted with a little CH2Cl2 until crystallisation occurs and diethyl ether was added. Solid was filtered, washed with diethyl ether and dried to afford N-(4-(6-chloro-[1,3]dioxolo[4,5-b]pyridin-7-ylamino)pyridin-2-yl)cyclopropanecarboxamide (15.00 g, 59.1 %) as a white powder. 1H NMR OK. |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C=C1)CN, amount is: 0.0008849999867379665 MOLE;aryl halide:C1CNC(=O)C2=C1C=C(C=C2)Br, amount is: 0.0002209999947808683 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0002209999947808683 MOLE,Solvents are Solvent:CN(C)C=O, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.1099999937869143e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.1099999937869143e-05 MOLE.Products are 0:C1CNC(=O)C2=C1C=C(C=C2)NCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 5 mL sealed MW* test tube was 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (50 mg, 0.22 mmol), phenylmethanamine (97 µl, 0.88 mmol), BINAP (6.89 mg, 0.01 mmol) and palladium(II) acetate (2.483 mg, 0.01 mmol) in DMF (500 mL) combined to give a tan suspension. potassium tert-butoxide (24.82 mg, 0.22 mmol) was then added last. Placed test tube onto Smith MW* platform. Heated reaction to 130°C for 4 minutes. Reaction know has a heavy black ppt present. Took LCMS - there is some product (~15%) beginning to form. Placed sealed test tube in heated (130°C) oil bath overnight. Took LCMS - all SM is consumed with a moderate product peak in evidence. Transferred reaction to separatory funnel. Partitioned reaction with EtOAc (40 ml) and water (25 ml). Separated off aq layer. Washed with sat NaCl. The organic was dried MgSO4, filt and conc - pale yellow syrup, 02915-84-0. Dissolved sample in 100% MeOH, added 2 drops NH4OH to adjust pH of sample and filtered off insolubles. The residue was purified via Agilent prep HPLC: Gradient run of 20-95% MeOH/H2O with 10 mmol NH4CO3 buffer (pH 10) over 25 mins. Flow rate 40 ml/min at wavelength 220 nM collection. 250 X 21.2 mm Gemini Axia pakC18 10 micron column. Collected like fractions which were concentrated under pump vacuum. Yield is low but see a mixture of products by NMR. Spectra shows desired material plus dialkylation product. Will reset and scale up reaction but lower amount of benzylamine and try the MW* only. |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C=C1)CN, amount is: 0.0002209999947808683 MOLE;aryl halide:C1CNC(=O)C2=C1C=C(C=C2)Br, amount is: 0.0002209999947808683 MOLE,Reagents are Base:C[O-].[Na+], amount is: 2.209999911428895e-05 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(CCP(C2=CC=CC=C2)C3=CC=CC=C3)C4=CC=CC=C4, amount is: 2.209999911428895e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.1099999937869143e-05 MOLE.Products are 0:C1CNC(=O)C2=C1C=C(C=C2)NCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a small MW* sealed test tube was 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (50 mg, 0.22 mmol), phenylmethanamine (24.16 µl, 0.22 mmol), palladium(II) acetate (2.483 mg, 0.01 mmol), Ethylenebis(diphenylphosphine) (8.81 mg, 0.02 mmol) and sodium methoxide (13.14 mg, 0.24 mmol) in toluene (2188 µl) combined to give a orange suspension. Heated reaction to 100°C overnight. Took LCMS - No reaction, only see unreacted SM. Discarded reaction. |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C=C1)CN, amount is: 0.0008849999867379665 MOLE;aryl halide:C1CNC(=O)C2=C1C=C(C=C2)Br, amount is: 0.0004419999895617366 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0004419999895617366 MOLE,Solvents are Solvent:CN(C)C=O, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.209999911428895e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.209999911428895e-05 MOLE.Products are 0:C1CNC(=O)C2=C1C=C(C=C2)NCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **Repeat 02915-84 but use MW* only. Reduce benzylamine from 4 to 2 eqs.** In a 10 mL sealed MW* test tube was 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.44 mmol), phenylmethanamine (97 µl, 0.88 mmol), BINAP (13.77 mg, 0.02 mmol) and palladium(II) acetate (4.97 mg, 0.02 mmol) in DMF (500 mL) combined to give a tan suspension. potassium tert-butoxide (49.6 mg, 0.44 mmol) was then added last. Placed test tube onto Smith MW* platform. Heated reaction to 130°C for 15 minutes. Reaction know a cloudy pale amber. Took LCMS - there is NO product present, ALL SM!!! Placed sealed test tube in heated (130°C) oil bath over weekend. Took LCMS - all SM is consumed but NO desired product is seen!!! Discarded reaction. |
Here is a chemical reaction formula: Reactants are aryl halide:C1CNC(=O)C2=C1C=C(C=C2)Br, amount is: 0.0002209999947808683 MOLE;amine:C1=CC=C(C=C1)CN, amount is: 0.0008849999867379665 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0002209999947808683 MOLE,this reaction does not need solvents,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.1099999937869143e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.1099999937869143e-05 MOLE.Products are 0:C1CNC(=O)C2=C1C=C(C=C2)NCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **Repeat 02915-84 but use NO solvent** In a 5 mL sealed MW* test tube was 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (50 mg, 0.22 mmol), phenylmethanamine (97 µl, 0.88 mmol), BINAP (6.89 mg, 0.01 mmol) and palladium(II) acetate (2.483 mg, 0.01 mmol) combined to give a tan suspension. potassium tert-butoxide (24.82 mg, 0.22 mmol) was then added last. Placed test tube onto Smith MW* platform. Heated reaction to 70°C for 5 minutes. NO reaction!!! Added DMF (0.5 ml) and reheated reaction to 130°C for 15 mins. Took LCMS - no reaction, only unreacted SM!! Discarded reaction. |
Here is a chemical reaction formula: Reactants are aryl halide:CC(C)OCC1CN(CC2=C(O1)N=C(C=C2)Cl)C(=O)C, amount is: 0.0005660000024363399 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0005660000024363399 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0017000000225380063 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 5.660000169882551e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 5.660000169882551e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)COC(C)C)C(=O)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 1-(8-chloro-2-(isopropoxymethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanone (0.169 g, 0.57 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.115 g, 0.57 mmol), Palladium acetate (0.013 g, 0.06 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.020 g, 0.06 mmol) and Cesium carbonate (0.553 g, 1.70 mmol) were placed in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (5 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. No product. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. Reaction still not complete. Added 0.1 eq ligand and palladium aceate, flushed with argon and run in the microwave at 100°C for 60 min. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and the residue was partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was separated by a Phase Separator and concentrated giving 1-(2-(isopropoxymethyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanone (0.039 g, 14.66 %). |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C(=C1)N)Cl, amount is: 0.02500000037252903 MOLE;aryl halide:C1=CC(=C(C=C1Br)F)C#N, amount is: 0.02500000037252903 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.05000000074505806 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0037499999161809683 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0024999999441206455 MOLE.Products are 0:C1=CC=C(C(=C1)NC2=CC(=C(C=C2)C#N)F)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.561 g, 2.50 mmol) and rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (2.335 g, 3.75 mmol) was added to a stirred slurry of 2-chloroaniline (2.63 mL, 25.00 mmol), 4-bromo-2-fluorobenzonitrile (5 g, 25.00 mmol) and cesium carbonate (16.29 g, 50.00 mmol) in toluene (180 mL) at 23°Cunder nitrogen. The resulting slurry was stirred at 80 °C for 2 hours. The reaction was incomplete (both SM left) so the temperature was increased to 100°C and the reaction mixture was stirred for a further 2 hours. The reaction was incomplete and further Palladium(II) acetate (100mg), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (400mg) and cesium carbonate (3g) were added and the slurry was stirred at 100 °C for a further 3 hours. Only small amount of 2 SM left and more product being formed. So further Palladium(II) acetate (100mg), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (400mg) and cesium carbonate (3g) were added and the slurry was stirred at 100 °C for a further 6 hours. traces of SM left The reaction mixture was filtered through PTFE, diluted with DCM (100 mL), and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford product as a pale yellow solid. LCMS showed 97% pure and 3% aniline. It was resuspended in DCM and the precipitate was collected by filtration, washed with DCM (10 mL) and dried under vacuum to afford 4-(2-chlorophenylamino)-2-fluorobenzonitrile (5.15 g, 84 %) as a white solid. EN03289-99-01 (2.75 g, 11.15 mmol, 44.6 %) Filtrate repurified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 4-(2-chlorophenylamino)-2-fluorobenzonitrile (5.15 g, 84 %) as a pale yellow solid. (pic 2) EN03289-99-02 (0.760 g, 3.08 mmol, 12.32 %) Pic 1 from column gave compound not 100% pure. Therefore it was triturated with isohexane to give a solid which was collected by filtration and dried under vacuum to give 4-(2-chlorophenylamino)-2-fluorobenzonitrile (5.15 g, 84 %) as a pale yellow solid. EN03289-99-03 (1.64 g, 6.65 mmol, 26.6 %) mixed fractions not kept as small amount. 1H NMR (400 MHz, DMSO) d 6.63 - 6.77 (2H, m), 7.21 - 7.30 (1H, m), 7.39 (1H, m), 7.46 (1H, m), 7.54 - 7.69 (2H, m), 8.99 (1H, s). m/z (ES-), (M-H)- = 245-247; HPLC tR = 2.62 min (acid and basic) |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=CN=C(N=C1C2=C3C=CC=CN3N=C2)Cl, amount is: 0.001550000044517219 MOLE;amine:CC(=O)N1CCC2=CC(=C(C=C21)N)OC, amount is: 0.001550000044517219 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0023300000466406345 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00015500000154133886 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00015500000154133886 MOLE.Products are 0:CC1=CN=C(N=C1C2=C3C=CC=CN3N=C2)NC4=C(C=C5CCN(C5=C4)C(=O)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 3-(2-chloro-5-methylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine (400 mg, 1.55 mmol), 1-(6-amino-5-methoxyindolin-1-yl)ethanone (341 mg, 1.55 mmol) and diacetoxypalladium (34.9 mg, 0.16 mmol) 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (97 mg, 0.16 mmol) cesium carbonate (759 mg, 2.33 mmol) were degassed with nitrogen then dioxane (7 mL) was added to mixture and the solution was degassed under vacuum and placed under nitrogen. The resulting suspension was stirred at 90 °C for 5hours. Control uplc/ms OK Control t.l.c : 100%EtOAc and 5%MeOH/CH2Cl2 After cooling, the mixture was filtered and the filtrate evaporated to dryness after addition of silica gel The crude product was purified by flash chromatography on silica gel 45g Merck column solid injectioneluting with 0 to 10%MeOH/EtOAc. The solvent was evaporated to dryness to afford 1-(5-methoxy-6-(5-methyl-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-ylamino)indolin-1-yl)ethanone (301 mg, 46.8 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C(=C1)C2CN(CC3=C(O2)N=C(C=C3)Cl)CC#N)C, amount is: 0.0003370000049471855 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0003370000049471855 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0010100000072270632 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 3.369999831193127e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.369999831193127e-05 MOLE.Products are 0:CC1=NN(C(=C1)C2CN(CC3=C(O2)N=C(C=C3)NC4=CC(=C(C=C4)N5C=C(N=C5)C)OC)CC#N)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.068 g, 0.34 mmol),2-(8-chloro-2-(1,3-dimethyl-1H-pyrazol-5-yl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (0.107 g, 0.34 mmol) Palladium acetate (7.56 mg, 0.03 mmol) and Cesium carbonate (0.329 g, 1.01 mmol) were added in a microwave vial. The mixture was capped and flushed with argon.1,2-dimethoxyethane (5 mL) was added, the reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. Reaction complete. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and the residue was partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was separated by a Phase Separator and concentrated giving 2-(2-(1,3-dimethyl-1H-pyrazol-5-yl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (0.027 g, 16.55 %). |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I, amount is: 0.0016299999551847577 MOLE;amine:CONC(=O)C1=C(C=CC(=C1)F)N, amount is: 0.0016799999866634607 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019600000232458115 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0002610000083222985 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00013099999341648072 MOLE.Products are 0:CONC(=O)C1=C(C=CC(=C1)F)NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (0.502 g, 1.63 mmol), 2-amino-5-fluoro-N-methoxybenzamide (0.344 g, 1.68 mmol), diacetoxypalladium (0.029 g, 0.13 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.151 g, 0.26 mmol) and cesium carbonate (0.638 g, 1.96 mmol) were weighed out in a microwave vial and sealed. dioxane (10.31 ml) was added and argon was let to bubble through the reaction mixture then it was stirred at 90 °C for 5 hours. The reaction mixture was allowed to cool to room temperature, silca gel was added and the mixture was concentrated to afford the crude, which was purified by flash chromatography on silica gel eluting with 20 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro-N-methoxybenzamide (0.240 g, 40.4 %) as an yellow oil which crystallised on standing. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0002880000101868063 MOLE;amine:CONC(=O)C1=C(C=C(C=C1)F)N, amount is: 0.0004889999981969595 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 4.320000152802095e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.320000152802095e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.59000007645227e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C=CC(=C3)F)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (24.98 mg, 0.04 mmol), diacetoxypalladium (5.82 mg, 0.03 mmol), 2-amino-4-fluoro-N- methoxybenzamide (90 mg, 0.49 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (110 mg, 0.29 mmol) and cesium carbonate (188 mg, 0.58 mmol) were weighed out in a µwave vial, sealed and dioxane (3 mL) was added. Argon was let to bubble in the mixture for 5 minutes. The reaction was stirred at 95 °C for 6h. The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane, silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (25g) eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness. The residue was triturated in tBuOMe (a bit soluble and soluble in diethyl ether) and the resulting precipitate was collected by filtration and dried to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methoxybenzamide (50.0 mg, 39.6 %) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0009599999757483602 MOLE;aryl halide:C1[C@H](OC2=C(CN1CC#N)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.0009599999757483602 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0028800000436604023 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 9.600000339560211e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.600000339560211e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)CC#N)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (195 mg, 0.96 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (288 mg, 0.96 mmol) Palladium acetate (21.55 mg, 0.10 mmol) and Cesium carbonate (938 mg, 2.88 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (5 mL) was added, the reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. Only after two additional additions of catalyst and ligand with 3h extra runtime was the reaction complete. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography 3 times yielding (R)-2-(8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (35.0 mg, 7.81 %). |
Here is a chemical reaction formula: Reactants are aryl halide:C1[C@H](OC2=C(CN1CCO)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.0003279999946244061 MOLE;amine:CC1=NN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0003279999946244061 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009840000420808792 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 3.279999873484485e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.279999873484485e-05 MOLE.Products are 0:CC1=NN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)CCO)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (67.0 mg, 0.33 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (100 mg, 0.33 mmol), Palladium acetate (7.37 mg, 0.03 mmol), 2-(Dicyclohexylphosphino)biphenyl (11.50 mg, 0.03 mmol) and Cesium carbonate (321 mg, 0.98 mmol) were added to a microwave vial. 1,2-dimethoxyethane (2 mL) was added. The reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. No product was observed. Additional catalyst and ligand were added and the reaction was run 1h @ 100°C. Still no reaction occurred. EtOH (0.500 mL) was added and another h @ 100°C was executed. Full conversion into product was observed. The solids were filtered off and the solvent was concentrated. The crude product was purified twice on Si. 20-80% MeOH in DCM. Yield: (R)-2-(8-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (33.0 mg, 21.28 %). |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(N=C1)Cl, amount is: 0.0004920000210404396 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0004920000210404396 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0014799999771639705 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 4.9199999921256676e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 4.9199999921256676e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=CC=N3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-Chloropyrimidine (0.056 g, 0.49 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.100 g, 0.49 mmol), Palladium acetate (0.011 g, 0.05 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.017 g, 0.05 mmol) and Cesium carbonate (0.481 g, 1.48 mmol) were placed in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (5 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. Very little product. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. No change. Seems as if the 2-chloropyrimidine is not very soluble in DME. Added 1.5 mL DMF and the reaction was run again in the microwave for 60 minutes. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and the residue was partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was separated by a Phase Separator and concentrated giving N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)pyrimidin-2-amine (0.026 g, 18.78 %). |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(C=C1CO)Cl, amount is: 0.0006970000104047358 MOLE;amine:CNC1=CC=C(C=C1)F, amount is: 0.0007660000119358301 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0028800000436604023 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 6.969999958528206e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.479999941191636e-05 MOLE.Products are 0:CN(C1=CC=C(C=C1)F)C2=NC=CC(=C2)CO, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask (t=g) was (2-chloropyridin-4-yl)methanol (.1 g, 0.70 mmol), Pd2dba3 (0.032 g, 0.03 mmol), and biphenyl-2-yldicyclohexylphosphine (0.024 g, 0.07 mmol) in toluene (6 mL) to give a dark red solution. 4-fluoro-N-methylaniline (0.096 g, 0.77 mmol) and KOtBu (.323 g, 2.88 mmol) were added. Mixture was degassed by bubbling N2 for 20 minutes, then placed in oil bath at 105 °C. Reaction went for 3 hours, at which point LC/MS was taken. No product was observed. |
Here is a chemical reaction formula: Reactants are amine:CNC1=CC=C(C=C1)F, amount is: 0.00039999998989515007 MOLE;aryl halide:C1=C(C=NC=C1Br)Br, amount is: 0.00047900000936351717 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0005990000208839774 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 5.990000136080198e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 1.9999999494757503e-05 MOLE.Products are 0:CN(C1=CC=C(C=C1)F)C2=CC(=CN=C2)Br, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask (t=g) was 4-fluoro-N-methylaniline (.05 g, 0.40 mmol), 3,5-dibromopyridine (0.114 g, 0.48 mmol), and Pd2(dba)3 (0.018 g, 0.02 mmol) in toluene (16 mL) ([VOLUME]) to give a purple suspension. biphenyl-2-yldicyclohexylphosphine (0.021 g, 0.06 mmol) and CS2CO3 (0.195 g, 0.60 mmol) were added. After LC/MS indicated no reaction had taken place at room temp, the temperature was gradually rasied to up to 110 degrees. LC/MS indicated that the reaction was not progressing. Reaction was discarded. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=NC=C1Br)Br, amount is: 0.009589999914169312 MOLE;amine:CNC1=CC=C(C=C1)F, amount is: 0.00798999983817339 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.010400000028312206 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 0.0012000000569969416 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00039999998989515007 MOLE.Products are 0:CN(C1=CC=C(C=C1)F)C2=CC(=CN=C2)Br, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask (t=g) was 4-fluoro-N-methylaniline (1 g, 7.99 mmol), 3,5-dibromopyridine (2.272 g, 9.59 mmol), and Pd2(dba)3 (0.366 g, 0.40 mmol) in toluene (16 mL) ([VOLUME]) to give a purple suspension. biphenyl-2-yldicyclohexylphosphine (0.420 g, 1.20 mmol) and KOtBu (1.166 g, 10.39 mmol) were added. Reaction was allowed to stir for 1.5 hours at which point LC/MS was taken which indicated that all the dibromopyridine had been consumed. Reaction was quenched by addition of excess ammonium chloride. Mixture was filtered though a plug of celite, extracted with ethyl acetate. The organic fractions were collected and washed with water, then dried over NaSO4, rotovapped down to an oil, redissolved in DCM then purified over a 120g column using 5 minutes of pure hexane, followed by a 0-50% EtOAc gradient (product comes off at around 35%). The relevant fractions were collected and rotovapped down yielding the product as an oil. |
Here is a chemical reaction formula: Reactants are aryl halide:CS(=O)(=O)C1=CC=C(C=C1)Br, amount is: 0.006000000052154064 MOLE;amine:C1=C(N=C(C=N1)Cl)N, amount is: 0.006000000052154064 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0004799999878741801 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0004799999878741801 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00023999999393709004 MOLE.Products are 0:CS(=O)(=O)C1=CC=C(C=C1)NC2=CN=CC(=N2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _1-bromo-4-(methylsulfonyl)benzene (1410 mg, 6.00 mmol)_ _then_ _cesium carbonate (2540 mg, 7.80 mmol)_ _ were successively added to a solution of __6-chloropyrazin-2-amine (777 mg, 6.00 mmol)_ _ _ _1,4-dioxane (20 ml)_ _into a microwave reactor._ _The mixture was purged by bubbling nitrogen for 5 minutes, then_ ___(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (278 mg, 0.48 mmol)_ _and_ _diacetoxypalladium (53.9 mg, 0.24 mmol)_ _were added , the mixture was degassed by vacuum/nitrogen three times, then heated to _ _75 °C_ _in an heating block( internal temperature )for 1 hr then at_ _85 °C_ _ and finally at __90 °C_ _for 30 min_ _After cooling the mixture was diluted with ethylacetate , filtered , the solid washed with ethyl acetate, and the organic solution washed with water, pre-dried with brine and dried over MgSO4 , filtrated and concentrated in vacuo.The solid was taken up with ethylacetate ( 20 ml) stirred 15 min , and diluted with diethylether until some trouble occured; the solid was filtered and the procedure was repeated.The solid was dried under vacuum ( 1 mmHg/1 hr /50°C ) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (1000 mg, 58.8%)_ _. The filtrate was concentrated and the above purification procedure was repeated three times to afford a second batch __6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (0.200 mg, 11.75 %) of the same purity . The 2 batches were combined to afford _ _6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (1200 mg, 70.5 %)_ _as a beige solid_ |
Here is a chemical reaction formula: Reactants are aryl halide:CS(=O)(=O)C1=CC=C(C=C1)Br, amount is: 0.019999999552965164 MOLE;amine:C1=C(N=C(C=N1)Cl)N, amount is: 0.019999999552965164 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0008800000068731606 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0008800000068731606 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0004400000034365803 MOLE.Products are 0:CS(=O)(=O)C1=CC=C(C=C1)NC2=CN=CC(=N2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _1-bromo-4-(methylsulfonyl)benzene (4.70 g, 19.99 mmol)_ _then_ _cesium carbonate (8.47 g, 25.99 mmol)_ _ were successively added to a solution of __6-chloropyrazin-2-amine (2.59 g, 19.99 mmol)_ _ _ _1,4-dioxane (75 ml)_ _into a microwave reactor._ _The mixture was purged by bubbling nitrogen for 5 minutes, then_ ___(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.509 g, 0.88 mmol)_ _and_ _diacetoxypalladium (0.099 g, 0.44 mmol)_ _were added , the mixture was degassed by vacuum/nitrogen three times, then heated to _ _80 °C_ _in an heating block for 2 hours then at __90 °C_ _for 30 min and a further 1 hour heating at __85 °C_ _._ After cooling the mixture was diluted with ethylacetate , filtered , the solid washed with ethyl acetate, the organic solution was washed with water, pre- dried with brine and dried over MgSO4 , filtrated and concentrated in vacuo.The solid was taken up with ethylacetate ( 50 ml) stirred 15 min , and diluted with diethylether until some trouble occured; the solid was filtered and the procedure was repeated twice The solid was dried under vacuum ( 1 mmHg/1 hr /50°C ) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (3. 15g, 55.5% , purity uv 98.6% ). The filtrate was concentrated and purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane. The solvent was evaporated to dryness to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (1.95 g,34.4% uv purity 94.6%) as a white solid. Nevertheless the 2 batches were combined to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (5.10 g, 90 %) |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=C(C(=CC=C1)C)C(=O)NC(C2=CC=C(C=C2)Br)C34CCC(N3C)CC4, amount is: 0.00023400000645779073 MOLE;amine:C1COCCN1, amount is: 0.0009360000258311629 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.00046800001291558146 MOLE,Solvents are Solvent:CN(C)C=O, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.3399999918183312e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.3399999918183312e-05 MOLE.Products are 0:CC1=C(C(=CC=C1)C)C(=O)NC(C2=CC=C(C=C2)N3CCOCC3)C45CCC(N4C)CC5, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a CEM microwave vial was N-((4-bromophenyl)(7-methyl-7-azabicyclo[2.2.1]heptan-1-yl)methyl)-2,6-dimethylbenzamide (100 mg, 0.23 mmol), morpholine (0.082 mL, 0.94 mmol), palladium(II) acetate (5.25 mg, 0.02 mmol), BINAP (14.57 mg, 0.02 mmol), and potassium tert-butoxide (52.5 mg, 0.47 mmol) solid and DMF (2 mL) was added. The vial was capped and placed into the microwave at 300 watts, 130 °C for 4 minutes. After reaction completion, the the mixture was concentrated and crude taken up in CH2Cl2 and washed with water and dried (Na2SO4). The material was purified on a 12 gram Isco silica cartridge and eluted with 0% to 5% MeOH 2M NH3/CH2Cl2 to give a light yellowish solid 2,6-dimethyl-N-((7-methyl-7-azabicyclo[2.2.1]heptan-1-yl)(4-morpholinophenyl)methyl)benzamide (30.0 mg, 29.6 %). |
Here is a chemical reaction formula: Reactants are aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3CC3, amount is: 0.0012199999764561653 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0012199999764561653 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0012199999764561653 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 0.00012199999764561653 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00012199999764561653 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5CC5)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.249 g, 1.22 mmol), 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.292 g, 1.22 mmol), Palladium acetate (0.027 g, 0.12 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.043 g, 0.12 mmol) and Cesium carbonate (0.399 g, 1.22 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (4 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. No product, only unreacted startingmaterial. Added 1 eq CsCO3, and 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. 9% product according to LCMS. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. No change. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. No change. Decided to isolate the intermediate and eventual product. The reaction mixture was filtrated through celite and concentrated. The crude was purified by preparative chromatography. The little product- containing fractions were collected but HPLC showed that they were not pure. The solvent was evaporated and the crude was partitioned between dichloromethane and sat. NaHCO3 (aq). The organic layer was separated with a phase separator and concentrated. Have 3 mg which is not pure. Discarded. Fractions with the intermediate 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine was collected, concentrated and the residue was partitioned with dichloromethane and sat. NaHCO3 (aq). The organic layer was separated, dried (Na2SO4) and concentrated giving 0.036 g of 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3CC3, amount is: 0.00015100000018719584 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.00015100000018719584 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00015100000018719584 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 1.5100000382517464e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.5100000382517464e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5CC5)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.031 g, 0.15 mmol), 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.036 g, 0.15 mmol), Palladium acetate (3.39 mg, 0.02 mmol), 2-(Dicyclohexylphosphino)biphenyl (5.29 mg, 0.02 mmol) and Cesium carbonate (0.049 g, 0.15 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (2 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. Extremely little product was formed according to LCMS and all oxazepinestartingmaterial was consumed. Did not isolate, discarded. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3CC3, amount is: 0.0009299999801442027 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0009299999801442027 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009299999801442027 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 9.300000237999484e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.300000237999484e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC4=C(CN(CC(O4)C5CC5)C)C=C3)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.189 g, 0.93 mmol), 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.222 g, 0.93 mmol), Palladium acetate (0.021 g, 0.09 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.033 g, 0.09 mmol) and Cesium carbonate (0.303 g, 0.93 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (2 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. Extremely little product was formed according to LCMS. Added 0.1 eq of Palladium acetate and 2-(Dicyclohexylphosphino)biphenyl and 1 eq Cesium carbonate and let run for another 60 min at 100°C in the microwave. According to LCMS ther is 13% startingmaterial oxazepine left. Added a small spatula of acetoxy(2'-(di-tert- butylphosphino)biphenyl-2-yl)palladium and 0.3 mL ethanol and let run for 30 minutes at 100°C. The reaction mixture was filtrated through celite and concentrated. The crude product was purified by silica flash chromatography using a gradient of metanol (+ 10%7M ammonia) in dichloromethane. Unreacted starting material 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline came out together with the product. Obtained 0.203 mg of impure product (at 254 nm 18% pure, at 220 nm 28% pure, at 290 nm 60% pure). Combined this with EN03597-98-001 and EN03597-99-001 at EN03597-97-001. |
Here is a chemical reaction formula: Reactants are aryl halide:C1[C@H](OC2=C(CN1CCO)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.0004920000210404396 MOLE;amine:COC1=C(C=CC(=C1)N)C#N, amount is: 0.0004920000210404396 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0014799999771639705 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 4.9199999921256676e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 4.9199999921256676e-05 MOLE.Products are 0:COC1=C(C=CC(=C1)NC2=NC3=C(CN(C[C@H](O3)C4=CC=CC=C4)CCO)C=C2)C#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 4-amino-2-methoxybenzonitrile (72.9 mg, 0.49 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (150 mg, 0.49 mmol), Palladium acetate (11.05 mg, 0.05 mmol), 2-(Dicyclohexylphosphino)biphenyl (17.25 mg, 0.05 mmol)and Cesium carbonate (481 mg, 1.48 mmol) were added to a microwave vial. 1,2-dimethoxyethane (2 mL) and EtOH (0.500 mL) were added. The reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. The solvent was decanted and the solids were washed with 5ml DCM. The solvent was evaporated and the crude product was purified on Si, 0-6% MeOH in DCM, yielding (R)-4-(4-(2-hydroxyethyl)-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-ylamino)-2-methoxybenzonitrile (27.0 mg, 13.17 %) |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.003449999960139394 MOLE;aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.0036299999337643385 MOLE,Reagents are Base:C(=O)([O-])[O-].[K+].[K+], amount is: 0.005179999861866236 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00017299999308306724 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00010399999882793054 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Purpose: to examine scale-up of microwave conditions established in a previous experiment. Charged a round-bottom flask with a mixture of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.702 g, 3.45 mmol), (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (1.0 g, 3.63 mmol), palladium (II) acetate (0.023 g, 0.10 mmol), rac-BINAP (0.108 g, 0.17 mmol), potassium carbonate (0.716 g, 5.18 mmol), and toluene (20 mL). The atmosphere s inerted through nitrogen purge cycles, then heated at 120 °C or 16 hours. HPLC-UV shows the reaction is not as clean as in the microwave, and conversion is very poor. The contents were allowed to continue heating over the weekend, but although conversion improved, the mixture contained many impurities. Not progressed. name='[Samples]' index='0' field='Samples' type='field' length='9'/>ber-coloured foam. |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.00018099999579135329 MOLE;aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.00018099999579135329 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00021800000104121864 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 1.4000000192027073e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 5.440000222733943e-06 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (0.05 g, 0.18 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.037 g, 0.18 mmol) (0.65), PALLADIUM(II) ACETATE (1.221 mg, 5.44 µmol), CESIUM CARBONATE (0.071 g, 0.22 mmol) and Tri-tert- butylphosphonium tetrafluoriborate (0.0043 g, 0.014 mmol, 6 mol%) in 1 ml of dioxane was degaset over argone and heated in MW 120°C 30 min. 002 - 4.8% of conversion mixture was heated more in MW 140°C 30 min. 003 - 15% of conversion mixture was heated more in MW 160°C 30 min. Experiment was not progressed. |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.00018099999579135329 MOLE;aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.00018099999579135329 MOLE,Reagents are Base:CCC(C)(C)[O-].[Na+], amount is: 0.00019999999494757503 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 1.4000000192027073e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 5.440000222733943e-06 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (0.05 g, 0.18 mmol), PALLADIUM(II) ACETATE (1.221 mg, 5.44 µmol) (1.6), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.037 g, 0.18 mmol) (0.64), Tri-tert- butylphosphonium tetrafluoriborate (0.0043 g, 0.014 mmol, 6 mol%) and Na-t-amilate (0.022 g, 1.1 equ, 0.2 mmol) in 1 ml of dioxane was degaset over argone and heated in MW 120°C 30 min. No reaction. Experiment was not progressed. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.001449999981559813 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0013099999632686377 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0002899999963119626 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0002899999963119626 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0001449999981559813 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (400 mg, 1.45 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (265 mg, 1.31 mmol), Cesium carbonate (709 mg, 2.18 mmol), Palladium(II) acetate (32.6 mg, 0.15 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (168 mg, 0.29 mmol) were added to a microwave vial then dioxane (18 mL) was added. The reaction mixture was flushed with argon and then heated at 140°C for 60 min in a MW. The reaction mixture was filtered through celite and concentrated. The crude product was purified by silica flash chromatography using a gradient of methanol (0 to 5%) in dichloromethane. Not pure enough. The product was purified further with preparative chromatography. The productcontainíng product was collected and the methanol was evaporated off. The wather phase was extracted three times with dichloromethane, dried (Na2SO4) and concentrated giving (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine (195 mg, 30.4 %) as a dry film. |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0001049999991664663 MOLE;aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.0001049999991664663 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 1.4700000065204222e-05 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.4700000065204222e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 7.359999926848104e-06 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The aim is optimization. (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (29 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (21.38 mg, 0.11 mmol), Sodium tert-butoxide (15.16 mg, 0.16 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (9.17 mg, 0.01 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (6.74 mg, 7.36 µmol) were added to a microwave vial then toluene (1 mL) was added. The reaction mixture was flushed with nitrogen and the mixture was heated to 120°C for 45 min. Small amount of product was formed. Abandoned. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.0002969999914057553 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.00035700001171790063 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0011899999808520079 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 2.970000059576705e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.970000059576705e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Palladium(II) acetate (6.68 mg, 0.03 mmol), 2-(Dicyclohexylphosphino)biphenyl (10.42 mg, 0.03 mmol) and Cesium carbonate (0.388 g, 1.19 mmol) were put in a 5 mL microwave vial and sealed. The vial was flushed with argon. (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (0.082 g, 0.30 mmol) in DME (5 mL) was added to the vial. The reaction mixture was run in the microwave at 100°C for 60 minutes. Forgot the aniline! Added 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.086 g, 0.36 mmol) and a small spatula of Palladium(II) acetate and 2-(Dicyclohexylphosphino)biphenyl and the reaction mixture was run in the microwave for 60 minutes for 100°C. The reaction mixture was filtrated through celite, concentrated and purified first by preparative chromatography. The productcontaining fractions were pooled, concentrated and partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was washed with sat. NaHCO3 (aq), dried (Na2SO4) and concentrated giving (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine (9.00 mg, 6.84 %). |
Here is a chemical reaction formula: Reactants are amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.00010900000052060932 MOLE;aryl halide:CN1C[C@H](OC2=NC(=NC=C2C1)Cl)C3=CC=CC=C3, amount is: 0.00010900000052060932 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 2.1800000467919745e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 2.1800000467919745e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 1.0900000233959872e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The aim is optimization. (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (30 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (22.11 mg, 0.11 mmol), Cesium carbonate (53.2 mg, 0.16 mmol), [Reactants] and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (12.59 mg, 0.02 mmol) were added to a microwave vial then dioxane (1 mL) was added. The reaction mixture was flushed with nitrogen and then heated at 130°C for 45 min in a MW. Small amount of product, quite messy. Abandoned. |
Here is a chemical reaction formula: Reactants are aryl halide:C1[C@H](OC2=NC(=NC=C2CN1CCF)Cl)C3=CC=CC=C3, amount is: 0.0004090000002179295 MOLE;amine:CC1=CN(C=N1)C2=C(C=C(C=C2)N)OC, amount is: 0.0004910000134259462 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 4.0899998566601425e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 4.0899998566601425e-05 MOLE.Products are 0:CC1=CN(C=N1)C2=C(C=C(C=C2)NC3=NC=C4CN(C[C@H](OC4=N3)C5=CC=CC=C5)CCF)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.118 g, 0.49 mmol), Palladium(II) acetate (9.19 mg, 0.04 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.014 g, 0.04 mmol) and Cesium carbonate (0.00 µmol) were put in a 5 mL microwave vial and sealed and purged with argon. (R)-2-chloro-6-(2-fluoroethyl)-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (0.126 g, 0.41 mmol) in DME (5 mL) was added. The reaction mixture was run in the microwave at 100°C for 60 minutes. Reaction still not complete. Additional palladium(II)acetate and 2-(dicyclohexylphosphino)biphenyl (small spatula) and the reaction was run again in the microwave for 60 minutes. The reaction mixture was filtrated through celite, concentrated and purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was washed with brine, dried (NaSO4) and concentrated giving (R)-6-(2-fluoroethyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine (0.029 g, 14.93 %) as the product. |
Here is a chemical reaction formula: Reactants are amine:CC1=NC=CN1C2=CC=C(C=C2)N, amount is: 0.0006960000027902424 MOLE;aryl halide:CC1=NN(C(=C1)C2CN(CC3=C(O2)N=C(C=C3)Cl)CC#N)C, amount is: 0.0006329999887384474 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019000000320374966 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 6.330000178422779e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.330000178422779e-05 MOLE.Products are 0:CC1=NN(C(=C1)C2CN(CC3=C(O2)N=C(C=C3)NC4=CC=C(C=C4)N5C=CN=C5C)CC#N)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 4-(2-methyl-1H-imidazol-1-yl)aniline (0.121 g, 0.70 mmol), Palladium acetate (0.014 g, 0.06 mmol) and Cesium carbonate (0.618 g, 1.90 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 2-(8-chloro-2-(1,3-dimethyl-1H-pyrazol-5-yl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (0.201 g, 0.63 mmol) in 1,2-dimethoxyethane (5 mL) was added, the reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. No product, only unreacted startingmaterial. Added 1 eq CsCO3, and 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. Reaction complete. The reaction mixture was filtrated through Celite and washed with dichloromethane. The filtrate was concentrated and the crude product was purified by preparative chromatography. The productcontaining fractions were pooled, concentrated and the residue was partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was separated by a Phase Separator and concentrated giving 2-(2-(1,3-dimethyl-1H-pyrazol-5-yl)-8-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)acetonitrile (0.041 g, 14.26 %) |
Here is a chemical reaction formula: Reactants are aryl halide:C1[C@H](OC2=C(CN1CCO)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.00039400000241585076 MOLE;amine:C1=CC(=C(C=C1N)Cl)N2C=NC=N2, amount is: 0.00039400000241585076 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.001180000021122396 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 3.94000016967766e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.94000016967766e-05 MOLE.Products are 0:C1[C@H](OC2=C(CN1CCO)C=CC(=N2)NC3=CC(=C(C=C3)N4C=NC=N4)Cl)C5=CC=CC=C5, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-chloro-4-(1H-1,2,4-triazol-1-yl)aniline (77 mg, 0.39 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (120 mg, 0.39 mmol), Palladium acetate (8.84 mg, 0.04 mmol), 2-(Dicyclohexylphosphino)biphenyl (13.80 mg, 0.04 mmol)and Cesium carbonate (385 mg, 1.18 mmol) were added to a microwave vial. 1,2-dimethoxyethane (2 mL) and EtOH (0.500 mL) were added. The reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. The solvent was decanted and the solids were washed with DCM, 5ml. The solvent was then evaporated and the crude product was purified on prepHPLC yielding (R)-2-(8-(3-chloro-4-(1H-1,2,4-triazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (16.00 mg, 8.78 %) |
Here is a chemical reaction formula: Reactants are amine:C1=CN=C(N=C1N)Cl, amount is: 0.001930000027641654 MOLE;aryl halide:C1=CN=CC=C1I, amount is: 0.001930000027641654 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.002319999970495701 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe], amount is: 0.0001900000061141327 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0001500000071246177 MOLE.Products are 0:C1=CN=CC=C1NC2=NC(=NC=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (0.035 g, 0.15 mmol) was added to a mixture of 2-chloropyrimidin-4-amine (0.250 g, 1.93 mmol), 4-iodopyridine (0.396 g, 1.93 mmol), cesium carbonate (0.755 g, 2.32 mmol) and (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (0.105 g, 0.19 mmol) in 1,4-dioxane (10 mL) and the reaction mixture stirred for 18 hours at 80 °C under nitrogen. EtOAc (50ml) was added to the reaction mixture and then the organics washed with water (3 x 50ml), brine (50ml) and then dried over MgSO4. The organics were then evaporated in vacuo to give the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford 2-chloro-N-(pyridin-4-yl)pyrimidin-4-amine (0.181 g, 45.3 %) as an orange solid. |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.004999999888241291 MOLE;aryl halide:C1=CC(=CC=C1O)Br, amount is: 0.004999999888241291 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.010499999858438969 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.0005000000237487257 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0002500000118743628 MOLE.Products are 0:C1COCCN1C2=CC=C(C=C2)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 4-Bromophenol (865 mg, 5 mmol), Tris(dibenzylideneacetone)dipalladium(0) (229 mg, 0.25 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (238 mg, 0.50 mmol), Morpholine (0.437 mL, 5.00 mmol) and sodium tert-butoxide (1009 mg, 10.50 mmol) were stirred in toluene (5 mL) overnight at 100 °C. The mixture was allowed to cool to ambient temperature. Ethylacetate was added and the mixture was washed with aqueous NaHCO3 (satd.) and water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-2 % MeOH in DCM. The collected fraction were combined and the solvent was removed by rotary evaporation. 1H NMR in CDCl3 is consistent with desired product MS (m+1) = 180. HPLC Peak RT = 2.55 minutes is product. Purity = 96%. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=C(C(=C1)Br)OC=C2, amount is: 0.010200000368058681 MOLE;amine:CC(C)(C)OC(=O)N1CCNCC1, amount is: 0.010200000368058681 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.021299999207258224 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.001019999966956675 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0005080000264570117 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC=CC3=C2OC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 7-bromobenzofuran (2 g, 10.15 mmol), tert-Butyl 1-piperazinecarboxylate (1.891 g, 10.15 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.465 g, 0.51 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.484 g, 1.02 mmol) and sodium t-butoxide (1.856 mL, 21.32 mmol) were heated to 100 °C in toluene (10 mL) for 3h. The mixture was allowed to cool to ambient temperature. Ethylacetate was added and the mixture was filtered through Celite. The filtrate was concentrated and redissolved in ethylacetate. The organic mixture was washed with satd. aqueous Na2CO3 and brine. The organic phase was separated, dried over Na2CO3, filtered and the solvent removed by rotary evaporation. The crude product was redissolved in diethylether and loaded onto a silica gel column and eluted with 0-50% EtOAc in heptanes. The collected fractions were combined and the solvent removed by rotary evaporation to yield tert-butyl 4-(benzofuran-7-yl)piperazine-1-carboxylate (2.58 g, 84 %). MS (m+1) = 303. HPLC Peak RT = 5.97 minutes is product. Purity = 94%. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=C(C(=C1)Br)OC=C2, amount is: 0.0025400000158697367 MOLE;amine:CC(C)(C)OC(=O)N1CCNCC1, amount is: 0.0025400000158697367 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.005330000072717667 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.00025400001322850585 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00012700000661425292 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC=CC3=C2OC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 7-bromobenzofuran (500 mg, 2.54 mmol), tert-Butyl 1-piperazinecarboxylate (473 mg, 2.54 mmol), Tris(dibenzylideneacetone)dipalladium(0) (116 mg, 0.13 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (121 mg, 0.25 mmol) and sodium t-butoxide (0.464 mL, 5.33 mmol) were heated in toluene (2 mL) to 100 °C for 2h. The mixture was allowed to cool. Ethylacetate was added and the mixture was filtered through Celite. The filtrate was concentrated and redissolved in ethylacetate. The organic mixture was washed with satd. aqueous Na2CO3 and brine. The organic phase was separated, dried over Na2CO3, filtered and the solvent removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-2% MeOH in DCM and to a second silica gel column eluted with 0-100% EtOAc in heptane. The collected fractions were combined to yield tert-butyl 4-(benzofuran-7-yl)piperazine-1-carboxylate (560 mg, 73.0 %). 1H NMR in CD3OD is consistent with desired product MS (m+1) = 303.1. HPLC Peak RT = 5.99 minutes is product. Purity = 98%. |
Here is a chemical reaction formula: Reactants are amine:C1CC2=NN=C(N2C1)C3=CC=C(C=C3)N, amount is: 0.00039400000241585076 MOLE;aryl halide:C1[C@H](OC2=C(CN1CCO)C=CC(=N2)Cl)C3=CC=CC=C3, amount is: 0.00039400000241585076 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.001180000021122396 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 3.94000016967766e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.94000016967766e-05 MOLE.Products are 0:C1CC2=NN=C(N2C1)C3=CC=C(C=C3)NC4=NC5=C(CN(C[C@H](O5)C6=CC=CC=C6)CCO)C=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 4-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)aniline (79 mg, 0.39 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (120 mg, 0.39 mmol) Palladium acetate (8.84 mg, 0.04 mmol), 2-(Dicyclohexylphosphino)biphenyl (13.80 mg, 0.04 mmol)and Cesium carbonate (385 mg, 1.18 mmol) were added to a microwave vial. 1,2-dimethoxyethane (2 mL) and EtOH (0.500 mL) were added. The reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. The crude product was taken up in DCM and the solids were thoroughly washed with DCM. The solvents were evaporated and the crude product was purified on Si. 0-20% MeOH in DCM with 2% triethylamine. Yield: (R)-2-(8-(4-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (39.0 mg, 21.14 %) |
Here is a chemical reaction formula: Reactants are aryl halide:COC(=O)C1=C(C=C(C=C1)I)O, amount is: 0.003599999938160181 MOLE;amine:CC(C)(C)OC(=O)N1CCNCC1, amount is: 0.003599999938160181 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007550000213086605 MOLE,Solvents are Solvent:COCCOC, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0003600000054575503 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00018000000272877514 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC(=C(C=C2)C(=O)OC)O, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl piperazine-1-carboxylate (0.670 g, 3.60 mmol) and methyl 2-hydroxy-4-iodobenzoate (1 g, 3.60 mmol), BINAP (0.224 g, 0.36 mmol), cesium carbonate (2.461 g, 7.55 mmol) were put inDME (18 mL), tris(dibenzylideneacetone)dipalladium(0) (0.165 g, 0.18 mmol) was added last. Reaction wsa purged by nitrogen, and heated at90 °C overnight. No desired product was found. |
Here is a chemical reaction formula: Reactants are amine:CONC(=O)C1=C(C=CC(=C1)F)N, amount is: 0.028699999675154686 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.019099999219179153 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.03819999843835831 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0019099999917671084 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0009549999958835542 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C=C(C=C3)F)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (7.3 g, 19.10 mmol), 2-amino-5-fluoro-N-methoxybenzamide (5.28 g, 28.66 mmol), diacetoxypalladium (0.214 g, 0.96 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.105 g, 1.91 mmol) and cesium carbonate (12.45 g, 38.21 mmol) were suspended in 1,4-dioxane (76 ml). The reaction was degased, purged with nitrogen and heated to 90°C (internal temperature) overnight _._ Reaction was concentrated to dryness. Residue was diluted with EtOAc (200 mL) and water (200 mL). Aqueous was extracted with EtOAc (100 mL) then with EtOAc/MeOH 9/1 (100 mL) => _aqueous still contained some expected product._ Aqueous was saturated with NaCl and extracted with EtOAc/MeOH 9/1 (100 mL). Combined organic layers were dried over MgSO4 and concentrated to dryness. The crude product (12g) was dissolved in CH2Cl2 (80 mL) for liquid injection but product started to precipitate. Solid was filtered and washed twice with CH2Cl2 to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro- N-methoxybenzamide (7.1 g) as an off-white solid. The filtrate was purified by flash chromatography on silica gel eluting with 10 to 100% ethyl acetate in dichloromethane ( _elution of impurities_ ) then with 5%, 10% and 15% MeOH in ethyl acetate ( _product elutes on TLC plate with 100% EtOAc but n MeOH to elute from the column probably due to poor solubility in EtOAc_ ). The solvent was evaporated to dryness. Residual oil was triturated in CH2Cl2. Resulting solid was filtered nad dried to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (0.9 g) as an off-white solid. Both batches (8g) were combined and recrystallised from EtOH (70 mL) to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (3.6 g) as a white crystalline solid => _less hot EtOH ( <60 mL ?) could have been used to solubilise all._ Filtrate was concentrated to ~half the volume and then stirred at room temperature for 4 hours. The resulting solid was filtered to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (3.2 g) as a white solid. Both batches of solid (6.8 g) were combined and slurried in EtOAc (65 mL) at room temperature for 24 hours. The resulting solid was filtered and dried at 50°C under high vacuum overnight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro- N-methoxybenzamide (4.52g, 54%, EN03787-13-01) as a white solid. Filtrate was concentrated to ~20 mL and then stirred at room temperature 24 hours. The resulting solid was filtered and dried under high vacuum at 50°C overnight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro- N-methoxybenzamide (1.12g, 13.4%, EN03787-13-02) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CONC(=O)C1=C(C=CC(=C1)F)N, amount is: 0.0003260000084992498 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00029600001289509237 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0005920000257901847 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 2.9599999834317714e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.4799999917158857e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C=C(C=C3)F)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (113 mg, 0.30 mmol), 2-amino-5-fluoro-N-methoxybenzamide (60 mg, 0.33 mmol) and Cesium carbonate (193 mg, 0.59 mmol) in degassed dioxane (4 mL) under nitrogen at room temperature were degassed (nitrogen) for a further 5 minutes before adding Palladium(II) acetate (3.32 mg, 0.01 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (17.14 mg, 0.03 mmol) the reaction mixture then being allowed to stir at 95 °C for 6 hours and cooled to RT. LCMS analysis showed a new peak for product (9%) but both SM's still remained (pyridine 71%, benzamide 13 %). Another 1.1 eq of benzamide (60 mg in 2ml dioxane) was added and the RM was then heated at 95 °C overnight. Lcms after this time showed no further progression with the reaction. Therefore a further portion of palladium acetate (0.05 eq. 3.32 mg) and the xanthene ligand (0.1 eq. 17.14 mg) were added and the RM stirred o/n at 95°C. Analysis after this time showed a majority peak for product and no pyridine SM remaining. The RM was concentrated and dry loaded onto silica. It was then purified on a 12g isco column using initially 0-100 % ethyl acetate in DCM followed by 0-10 % methanol in ethyl acetate to give 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro- N-methoxybenzamide (60.0 mg, 46.2 %) which was not very pure Trituration with diethyl ether did not produce a purer product. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0094200000166893 MOLE;amine:CONC(=O)C1=C(C=CC(=C1)F)N, amount is: 0.014100000262260437 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009420000133104622 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0009420000133104622 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0004710000066552311 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C=C(C=C3)F)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-amino-5-fluoro-N-methoxybenzamide (2.60 g, 14.13 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (3.6 g, 9.42 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.545 g, 0.94 mmol) diacetoxypalladium (0.106 g, 0.47 mmol) and cesium carbonate (6.14 g, 18.84 mmol) were suspended in dioxane (40 mL). The reaction was degased, purged with argon (3 times) and heated to 100 °C overnight. The reaction mixture was allowed to cool to room temperature under stirring, diluted with ethyl acetate and the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 15% methanol in ethyl acetate/DCM (1/1). Fractions containing the most part of pure product were evaporated. This residue was re-purified by trituration with DCM (with 5% MeOH), to give after filtration EN03299-42-01 (3.5 g, 7.98 mmol, 85 %) which contains trace of AcOEt and 30%mol DCM. The resulting solid was recrystallised from ethanol (35 ml) and the resulting crystalline solid was collected by filtration, washed with ethanol and dried to a constant weight in a vacuum oven to afford EN03299-42-02 (2.7 g, 5.54 mmol, 58.8 %) as a white crystalline solid. TSB 46.938 |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.009159999899566174 MOLE;amine:CNC(=O)C1=C(C=C(C=C1)F)N, amount is: 0.013700000010430813 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009159999899566174 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0009159999899566174 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0004579999949783087 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C=CC(=C3)F)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-amino-4-fluoro-N-methylbenzamide (2.310 g, 13.74 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (3.5 g, 9.16 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.530 g, 0.92 mmol) diacetoxypalladium (0.103 g, 0.46 mmol) and cesium carbonate (5.97 g, 18.32 mmol) were suspended in dioxane (40 mL). The reaction was degased, purged with argon (3 times) and heated to 100 °C for 5 hours. The reaction mixture was allowed to cool to room temperature under stirring, diluted with ethyl acetate and the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in ethyl acetate/DCM (1/1). Fractions containing pure product were evaporated to give a foam. This residue was triturated with DCM and filtered to afford EN03299-43-01 (1.4 g, 3.31 mmol, 36.2 %) as an off- white product. combined with APE-03299-48 700 mg of aniline was recovered |
Here is a chemical reaction formula: Reactants are amine:COC1=CC=CC(=C1C(=O)NOC)N, amount is: 0.00022200000239536166 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00013099999341648072 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00026199998683296144 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.3099999705445953e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.539999958476983e-06 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (50 mg, 0.13 mmol), 2-amino-N,6-dimethoxybenzamide (43.6 mg, 0.22 mmol), diacetoxypalladium (1.469 mg, 6.54 µmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (8.15 mg, 0.01 mmol) and cesium carbonate (85 mg, 0.26 mmol) were suspended in 1,4-dioxane (436 µl) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 90 °C overnight => _slow reaction, a few expected product formed, no des-iodo observed, both SM left_ **_NOT ISOLATED_** |
Here is a chemical reaction formula: Reactants are amine:COC1=CC=CC(=C1C(=O)NOC)N, amount is: 0.00022200000239536166 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00013099999341648072 MOLE,Reagents are Base:C(=O)([O-])[O-].[K+].[K+], amount is: 0.00026199998683296144 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.3099999705445953e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.539999958476983e-06 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (50 mg, 0.13 mmol), 2-amino-N,6-dimethoxybenzamide (43.6 mg, 0.22 mmol), diacetoxypalladium (1.469 mg, 6.54 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.57 mg, 0.01 mmol) and potassium carbonate (36.2 mg, 0.26 mmol) were suspended in 1,4-dioxane (423 µl) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 90 °C overnight => _not complete but seemed to be clean, no des-iodo by-product formed, both SM left_ Same reaction was performed in toluene (423 µl) => _reaction complete, LCMS profile similar to the conception document reference_ **_NOT ISOLATED_** |
Here is a chemical reaction formula: Reactants are amine:COC1=CC=CC(=C1C(=O)NOC)N, amount is: 0.10100000351667404 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.059700001031160355 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.005969999823719263 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.005969999823719263 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0029800001066178083 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (22.8 g, 59.67 mmol), 2-amino-N,6-dimethoxybenzamide (19.90 g, 101.43 mmol), diacetoxypalladium (0.670 g, 2.98 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.45 g, 5.97 mmol) and cesium carbonate (23.33 g, 71.60 mmol) were suspended in 1,4-dioxane (199 ml). The reaction was degased, purged with nitrogen and heated to 90 °C => _reaction turned to dark brown and solidified after ~15 minutes._ 1,4-dioxane (50 mL) was added and reaction was stirred at 90°C (internal temperature) overnight => _stirring became easier and mixture turned to beige/yellow then to dark green/grey during the night._ Reaction was concentrated to dryness. Residue was diluted with CH2Cl2 (300 mL) and water (300 mL). Aqueous was extracted with CH2Cl2 (100 mL) then with CH2Cl2/MeOH 9/1 (100 mL) => _aqueous still contained expected product._ Aqueous was saturated with NaCl and extracted with CH2Cl2/MeOH 9/1 (100 mL). Combined organic layers were dried over MgSO4 and concentrated to dryness. The crude product (38.5g) was dissolved in CH2Cl2 (100 mL) for liquid injection but some product started to precipitate. Solid was filtered and washed twice with CH2Cl2 to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (5.2 g) as a white solid. The filtrate was purified by flash chromatography on silica gel eluting with 0 to 7% methanol in ethyl acetate. The solvent was evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (20.6 g) as a beige solid. Both batches of product (25.8 g) were combined and triturated in tBuOMe (50 mL) / CH2Cl2 (20 mL). The resulting solid was filtered, washed with tBuOMe (50 mL) to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (23 g) as a white solid. It was suspended in H2O (350 mL) and stirred at room temperature overnight => _mixture solidified._ It was filtered and dried over P2O5 under high vacuum for 6 hours. The resulting solid was suspended in acetonitrile (460 mL) and stirred at room temperature over the weekend. It was filtered, washed with cold acetonitrile and dried under high vacuum at 50°C overnight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (8.4 g, 31.3%, EN03787-12-01) as a white solid => _product is quite soluble in acetonitrile, volume of solvent was too important (ref from PARD : 50mg in 1mL)_ Filtrate was concentrated to ~100 mL (= until preciptation occured on the rotavapor) and then stirred at room temperature for 4 hours. The resulting solid was filtered and dried under high vacuum at 50°C overnight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (9.3 g, 34.6%, EN03787-12-02) as a white solid. Filtrate was concentrated to dryness to afford another batch of impure product (2.8g) which was slurried in CH3CN (28 mL) at room temperature overnight. The resulting solid was filtered and dried under high vacuum at 50°C to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (1.54 g, 5.73%, EN03787-12-03) as a white solid => _this batch is less pure than the 2 others_ |
Here is a chemical reaction formula: Reactants are amine:COC1=CC=CC(=C1C(=O)NOC)N, amount is: 0.0013800000306218863 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0009169999975711107 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.001829999964684248 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 9.169999975711107e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 4.5900000259280205e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (351 mg, 0.92 mmol), 2-amino-N,6-dimethoxybenzamide (270 mg, 1.38 mmol) and Cesium carbonate (598 mg, 1.83 mmol) in degassed dioxane (8 mL) under nitrogen at room temperature were allowed to stir, degassing (nitrogen) for a further 5 minutes before adding Palladium(II) acetate (10.30 mg, 0.05 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (53.1 mg, 0.09 mmol). The reaction mixture was then stirred at 90 °C for 4 hours and cooled to RT. LCMS analysis showed a new peak for product but both SM's still remained. The RM was then heated at 100 °C for a further 4 hours, after this time LCMS analysis showed none of the pyridine SM remaining and a bigger peak for product. The RM was concentrated and then dissolved in methanol and dry loaded onto silica. The crude was purified on a 12g Si column eluting with 0-10 % methanol in DCM. Fractions 3-8 and 18-28 contained product and were combined. LCMS analysis/TLC showed that the product was still not pure. Diethyl ether trituration gave 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (235 mg, 56.9 %) as a pure product. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C, amount is: 0.030700000002980232 MOLE;aryl halide:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2C(F)(F)F)Cl, amount is: 0.025599999353289604 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.030700000002980232 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.004100000020116568 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.002050000010058284 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C=CC(=C3)F)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide (8.9 g, 25.60 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (3.41 g, 30.72 mmol), diacetoxypalladium (0.460 g, 2.05 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.370 g, 4.10 mmol) and cesium carbonate (10.01 g, 30.72 mmol) were suspended in 1,4-dioxane (111 ml). The reaction was degased, purged with nitrogen and heated to 90°C (internal temperature) for 4 hours _._ Reaction was concentrated to dryness. Residue was diluted with CH2Cl2/MeOH 9/1 (200 mL) and water (200 mL). Aqueous was extracted with CH2Cl2/MeOH 9/1 (100 mL). Combined organic layers were dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (7.6 g) as a yellow foam => _1H NMR showed that it contained EtOAc and a vey small amount of an impurity_. This residue was triturated in CH2Cl2 (10 mL) => _complete solubilisation followed by precipitation._ The resulting solid was filtered and washed with tBuOMe (10 mL) to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (6.3 g) as a pale yellow solid => _1H NMR showed that EtOAc and impurity has been removed_ This solid was suspended in tBuOMe (20 mL) and stirred at 50°C (heating block temperature) for 1 hour. Mixture was allowed to cool for 5 minutes then filtered, washed once with tBuOMe (10 mL) and dried overnight under high vacuum at 50°C to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (6.00 g, 55.5 %) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C, amount is: 0.006899999920278788 MOLE;aryl halide:CNC(=O)C1=C(C=C(C=C1)F)NC2=CC(=NC=C2C(F)(F)F)Cl, amount is: 0.005750000011175871 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.006899999920278788 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0009200000204145908 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0004600000102072954 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C=CC(=C3)F)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide (2 g, 5.75 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (0.767 g, 6.90 mmol) diacetoxypalladium (0.103 g, 0.46 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.533 g, 0.92 mmol) and cesium carbonate (2.249 g, 6.90 mmol) were suspended in dioxane (25 ml). The reaction was degased, purged with argon (3 times) and heated to at 90 °C for 4 hours. The reaction mixture was allowed to cool to room temperature, diluted with DCM (some drop of MeOH) and filtered. Silica gel was added and solvents were evaporated to afford the crude, which was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in ethyl acetate/DCM (1/1) . The solvent was evaporated to dryness to give a residue which was triturated with DCM, filtered and dried to afford EN03299-48-01 (1.5 g, 3.55 mmol, 61.7 %) as a off-white solid. This sample EN03299-48-01 (1.5 g, 3.55 mmol, 61.7 %) and _EN03299-43-01_ were combined and triturated with hot tBuOMe, filtered and dried to afford EN03299-48-02 (2.1 g, 4.90 mmol, 85 %) as a white solid. Trituration filtrates were evaporated and the residue was taken with DCM, filtered and dried to afford EN03299-48-03 (0.5 g, 1.184 mmol, 20.58 %) as a white solid TSB 46.916 |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(N=C(C=N1)Cl)Cl, amount is: 0.001930000027641654 MOLE;amine:CS(=O)(=O)C1=CC=C(C=C1)N, amount is: 0.001930000027641654 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0021200000774115324 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00019299999985378236 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00019299999985378236 MOLE.Products are 0:CS(=O)(=O)C1=CC=C(C=C1)NC2=CN=CC(=N2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2,6-dichloropyrazine (287 mg, 1.93 mmol), 4-(methylsulfonyl)aniline (330 mg, 1.93 mmol), diacetoxypalladium (43.3 mg, 0.19 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (120 mg, 0.19 mmol) and cesium carbonate (690 mg, 2.12 mmol) in 1,4-dioxane (2 mL) were degazed and stirred at 90 °C for 16 hours under nitrogen. The reaction mixture was evaporated to dryness and was purified by preparative HPLC using a Waters SunFire reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (120 mg, 21.95 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=CC(=CC=C1)Br, amount is: 0.05350000038743019 MOLE;amine:C1CNCCC1C#N, amount is: 0.06419999897480011 MOLE,Reagents are Base:[Li+].C[Si](C)(C)[N-][Si](C)(C)C, amount is: 0.12300000339746475 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.002139999996870756 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.010700000450015068 MOLE.Products are 0:COC1=CC=CC(=C1)N2CCC(CC2)C#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Reaction carried out by , work up and purification on this page. piperidine-4-carbonitrile (7.07 g, 64.16 mmol); 1-bromo-3-methoxybenzene (6.77 mL, 53.47 mmol) and diacetoxypalladium (2.401 g, 10.69 mmol) were thoroughly placed under an inert atmoshere. To this was added 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.732 g, 2.14 mmol); LITHIUM BIS(TRIMETHYLSILYL)AMIDE (123 mL, 122.97 mmol) and toluene (20 mL). The resultant mixture was stirred overnight at 100 °C (suspect that it did not need overnight. The reaction mixture was poured onto DCM (200 mL), the mixture was filtered through celite and evaporated to afford a black residue. This was suspended in EtOAc (200 mL) and water (20 mL) and filtered through a pad of silica, washing through with EtOAc (300 mL) and water (20 mL). The filtrate was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 1-(3-methoxyphenyl)piperidine-4-carbonitrile (3.29 g, 28.5 %) as a yellow oil which solidified on standing. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=CC(=CC=C1)Br, amount is: 0.0026700000744313 MOLE;amine:C1CNCCC1C#N, amount is: 0.0032099999953061342 MOLE,Reagents are Base:[Li+].C[Si](C)(C)[N-][Si](C)(C)C, amount is: 0.006149999797344208 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.00010699999984353781 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.000534999999217689 MOLE.Products are 0:COC1=CC=CC(=C1)N2CCC(CC2)C#N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: piperidine-4-carbonitrile (0.353 g, 3.21 mmol); 1-bromo-3-methoxybenzene (0.339 mL, 2.67 mmol) and diacetoxypalladium (0.120 g, 0.53 mmol) were thoroughly placed under an inert atmoshere. To this was added 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.037 g, 0.11 mmol); LITHIUM BIS(TRIMETHYLSILYL)AMIDE (6.15 mL, 6.15 mmol) and toluene (10 mL). The resultant mixture was stirred overnight at 100 °C (suspect that it did not need overnight. Equal vol of DCM was added and the reaction mixture filtered. Removal of the solvent under reduced pressure gave a dark brown gum. The crude product was purified by flash Silica chromatography {CombiFlash Companion - Presearch Ltd}, column size = 12 g , flow rate = 30 ml / min, elution gradient 0 to 30% EtOAc in isohexane over 10 minutes {excluding lead in & wash etc.}. Pure fractions were evaporated to dryness to afford 1-(3-methoxyphenyl)piperidine-4-carbonitrile (0.315 g, 54.5 %) as a tan brown solid. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=CC(=CC=C1)Br, amount is: 0.0026700000744313 MOLE;amine:C1CNCCC1C(=O)N, amount is: 0.0032099999953061342 MOLE,Reagents are Base:[Li+].C[Si](C)(C)[N-][Si](C)(C)C, amount is: 0.006149999797344208 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.00010699999984353781 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.000534999999217689 MOLE.Products are 0:COC1=CC=CC(=C1)N2CCC(CC2)C(=O)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: piperidine-4-carboxamide (0.411 g, 3.21 mmol); 1-bromo-3-methoxybenzene (0.339 mL, 2.67 mmol) and diacetoxypalladium (0.120 g, 0.53 mmol) were thoroughly placed under an inert atmoshere. To this was added 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.037 g, 0.11 mmol); LITHIUM BIS(TRIMETHYLSILYL)AMIDE (6.15 mL, 6.15 mmol) and toluene (10 mL). The resultant mixture was stirred at 100 °C overnight. No sign of reaction by LCMS overnight. Abandoned |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=C(C=C1[N+](=O)[O-])SC(=N2)Br, amount is: 0.003860000055283308 MOLE;amine:CN, amount is: 0.019300000742077827 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00046300000394694507 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00046300000394694507 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00019299999985378236 MOLE.Products are 0:CNC1=NC2=C(S1)C=C(C=C2)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: methanamine (0.793 mL, 19.30 mmol), 2-bromo-6-nitrobenzo[d]thiazole (1 g, 3.86 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.268 g, 0.46 mmol), cesium carbonate (1.886 g, 5.79 mmol) and diacetoxypalladium (0.043 g, 0.19 mmol) were suspended in 1,4-dioxane (8 mL) and sealed into a microwave tube. The reaction was heated to 150°C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford a crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% DCM in EtOAc. Pure fractions were evaporated to dryness to afford N-methyl-6-nitrobenzo[d]thiazol-2-amine (0.050 g, 6.19 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are amine:COC1=C(C=C(C=C1)[N+](=O)[O-])N, amount is: 0.00037900000461377203 MOLE;aryl halide:C1=CC=C2C(=C1)C(=CN2)C3=NC(=NC=C3Cl)Cl, amount is: 0.00037900000461377203 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 4.540000009001233e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.540000009001233e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.2700000045006163e-05 MOLE.Products are 0:COC1=C(C=C(C=C1)[N+](=O)[O-])NC2=NC=C(C(=N2)C3=CNC4=CC=CC=C43)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution of 3-(2,5-dichloropyrimidin-4-yl)-1H-indole (100 mg, 0.38 mmol) in dioxane (10 mL) was added 2-methoxy-5-nitroaniline (63.7 mg, 0.38 mmol), cesium carbonate (247 mg, 0.76 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (26.3 mg, 0.05 mmol). The resulting suspension was purged with nitrogen for 5 minutes. diacetoxypalladium (5.10 mg, 0.02 mmol) was added and the mixture was purged with nitrogen for a further 5 minutes, and then heated at 80 °C overnight. UPLC shows di-Cl SM almost completely consumed but no evidence of desired product. Reaction stopped |
Here is a chemical reaction formula: Reactants are amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, amount is: 0.0005089999758638442 MOLE;aryl halide:CC1=CC(=NC2=C1CN(CC(O2)CC(F)(F)F)C)Cl, amount is: 0.0005089999758638442 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 3.559999822755344e-05 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 3.559999822755344e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.559999822755344e-05 MOLE.Products are 0:CC1=CC(=NC2=C1CN(CC(O2)CC(F)(F)F)C)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (104 mg, 0.51 mmol), 8-chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (150 mg, 0.51 mmol), Sodium tert-butoxide (73.4 mg, 0.76 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (22.19 mg, 0.04 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (32.6 mg, 0.04 mmol) were added to a radley tube followed by toluene (6 mL). The reaction mixture was flushed with argon and the mixture was heated to 100°C and stirred overnight. The solids were filtered off and washed with DCM. The crude product was purified on prepHPLC yielding N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (23.00 mg, 9.77 %) |