4-溴-2-(三氟甲氧基)苯甲胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of ({4-bromo-2-[(trifluoromethyl)oxy]phenyl}methyl)amine (0.4 g, 1.041 mmol), 3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxylic acid (0.276 g, 1.041 mmol), 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.507 g, 1.146 mmol) and diisopropylethylamine (0.364 ml, 2.083 mmol) in N,N-Dimethylformamide (DMF) (5 ml) was stirred overnight at RT. The reaction mixture was treated with water which caused a precipitate to form. The precipitate was filtered and washed with water, and dried to give N-({4-bromo-2-[(trifluoromethyl)oxy]phenyl}methyl)-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (0.35 g, 0.543 mmol, 53%) as an off-white solid. MS (ES) m/e 517, 519 [M+H]+. to form The precipitate was filtered washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylic acid (100 mg, 0.4 mmol) was dissolved in 3 mL of dichloromethane and treated with EDCI (115 mg, 0.6 mmol), HOBt (65 mg, 0.48 mmol), triethylamine (0.44 mL, 3.2 mmol), and 1-{4-bromo-2-[(trifluoromethyl)oxy]phenyl}methanamine (152 mg, 0.4 mmol) at 8° C. for 4 days. The reaction mixture was concentrated and purified by preparative HPLC to provide N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxamide (3.5 mg, 0.02 mmol, 2%) as a white solid. MS (ES+): m/e 503, 505 [M+H]+. 1H NMR (400 MHz, methanol-D4) 7.4 (m, 2H), 7.2 (d, 1H), 4.8 (2H under MeOH peak), 4.3 (s, 2H), 3.1 (m, 2H), 2.9 (s, 3H), 2.5 (m, 1H), 2.3 (s, 3H), 1.8 (m, 2H), 1.6 (m, 2H) The reaction mixture was concentrated purified by preparative HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of ({4-bromo-2-[(trifluoromethyl)oxy]phenyl}methyl)amine (0.4 g, 1.041 mmol), 3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxylic acid (0.276 g, 1.041 mmol), 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.507 g, 1.146 mmol) and diisopropylethylamine (0.364 ml, 2.083 mmol) in N,N-Dimethylformamide (DMF) (5 ml) was stirred overnight at RT. The reaction mixture was treated with water which caused a precipitate to form. The precipitate was filtered and washed with water, and dried to give N-({4-bromo-2-[(trifluoromethyl)oxy]phenyl}methyl)-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (0.35 g, 0.543 mmol, 53%) as an off-white solid. MS (ES) m/e 517, 519 [M+H]+. to form The precipitate was filtered washed with water dried