4-bromo-N-cyclopropyl-2-methylbenzamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-N-cyclopropyl-2-methyl-benzamide (Intermediate 157, 1.81 g, 7.12 mmols) in THF (12 mL) was added BH3.SMe2 (1.08 g, 14.24 mmols). The solution was heated to 60° C. for 6 hours, cooled to room temperature and carefully treated with saturated aqueous Na2CO3 (30 mL) and stirred for 17 hours. This mixture was extracted with EtOAc and the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound was isolated by column chromatography (10-15% EtOAc-hexanes). cooled to room temperature This mixture was extracted with EtOAc the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-2-methylbenzoic acid and SOCl2 was refluxed for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 30 mL CH2Cl2 and combined with cyclopropyl amine (810.0 mg, 14.3 mmols) and pyridine (2.05 g, 26.0 mmols). The solution was stirred for 18 hours and then diluted with EtOAc before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl. The solution was dried (MgSO4) and concentrated under reduced pressure leaving the title compound as a colorless solid. concentrated under reduced pressure The residue was dissolved in 30 mL CH2Cl2 before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl The solution was dried (MgSO4) concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-N-cyclopropyl-2-methyl-benzamide (Intermediate 157, 1.81 g, 7.12 mmols) in THF (12 mL) was added BH3·SMe2 (1.08 g, 14.24 mmols). The solution was heated to 60° C. for 6 hours, cooled to room temperature and carefully treated with saturated aqueous Na2CO3 (30 mL) and stirred for 17 hours. This mixture was extracted with EtOAc and the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound was isolated by column chromatography (10-15% EtOAc-hexanes). cooled to room temperature This mixture was extracted with EtOAc the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-2-methylbenzoic acid and SOCl2 was refluxed for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 30 mL CH2Cl2 and combined with cyclopropyl amine (810.0 mg, 14.3 mmols) and pyridine (2.05 g, 26.0 mmols). The solution was stirred for 18 hours and then diluted with EtOAc before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl. The solution was dried (MgSO4) and concentrated under reduced pressure leaving the title compound as a colorless solid. concentrated under reduced pressure The residue was dissolved in 30 mL CH2Cl2 before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl The solution was dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-N-cyclopropyl-2-methyl-benzamide (Intermediate 157, 1.81 g, 7.12 mmols) in THF (12 mL) was added BH3.SMe2(1.08 g, 14.24 mmols). The solution was heated to 60° C. for 6 hours, cooled to room temperature and carefully treated with saturated aqueous Na2CO3(30 mL) and stirred for 17 hours. This mixture was extracted with EtOAc and the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound was isolated by column chromatography (10-15% EtOAc-hexanes). cooled to room temperature This mixture was extracted with EtOAc the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-N-cyclopropyl-2-methyl-benzamide (Intermediate 157, 1.81 g, 7.12 mmols) in THF (12 mL) was added BH3.SMe2(1.08 g, 14.24 mmols). The solution was heated to 60° C. for 6 hours, cooled to room temperature and carefully treated with saturated aqueous Na2CO3(30 mL) and stirred for 17 hours. This mixture was extracted with EtOAc and the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound was isolated by column chromatography (10-15% EtOAc-hexanes). cooled to room temperature This mixture was extracted with EtOAc the combined organic layers were washed with H2O, saturated aqueous NaCl before being dried (MgSO4) concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-N-cyclopropyl-2-methyl-benzamide (Intermediate 157, 1.81 g, 7.12 mmols) in THF (12 mL) was added BH3.SMe2 (1.08 g, 14.24 mmols). The solution was heated to 60° C. for 6 hours, cooled to room temperature and carefully treated with saturated aqueous Na2CO3 (30 mL) and stirred for 17 hours. This mixture was extracted with EtOAc and the combined organic layers were washed with H2O, saturated aqueous NaCi before being dried (MgSO4) and concentrated under reduced pressure. The title compound was isolated by column chromatography (10-15% EtOAc-hexanes). cooled to room temperature This mixture was extracted with EtOAc the combined organic layers were washed with H2O, saturated aqueous NaCi before being dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-2-methylbenzoic acid and SOCl2 was refluxed for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 30 mL CH2Cl2 and combined with cyclopropyl amine (810.0 mg, 14.3 mmols) and pyridine (2.05 g, 26.0 mmols). The solution was stirred for 18 hours and then diluted with EtOAc before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl. The solution was dried (MgSO4) and concentrated under reduced pressure leaving the title compound as a colorless solid. concentrated under reduced pressure The residue was dissolved in 30 mL CH2Cl2 before being washed with 5% aqueous HCl, saturated NaHCO3, and saturated aqueous NaCl The solution was dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-2-methylbenzoic acid (300 g, 1.4 mol) in DCM (8.4 L) at rt was added cyclopropanamine (79.64 g, 1.4 mol) and EDC (320.9 g, 1.67 mol) in one portion. After stirring overnight, the solution was washed with water and the aqueous phase was reextracted with DCM. The combined organic phases were dried over sodium sulfate, filtered and evaporated. The remaining solid was triturated with diisopropyl ether, filtered, washed and dried in vaccuo to yield 260 g (73.4%) 4-bromo-N-cyclopropyl-2-methylbenzamide. the solution was washed with water The combined organic phases were dried over sodium sulfate filtered evaporated The remaining solid was triturated with diisopropyl ether filtered washed dried in vaccuo