反应详情

温度

60 °C

Methyl (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-L-prolinate (Intermediate 10, 42 mg, 0.066 mmol) was dissolved in 7N ammonia solution in MeOH (3 ml, 21.0 mmol) and the reaction mixture was stirred for 48 hours at 60° C. The solvent was evaporated and the residue was purified by flash chromatography on silica gel (Companion system; eluent: from 99:1 Dichloromethane/MeOH to 95:5 Dichloromethane/MeOH; 12 g cartridge) affording the title compound (28 mg, 0.045 mmol, 68.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (s, 1H) 8.04 (s, 1H) 7.89-7.99 (m, 1H) 7.60-7.87 (m, 2H) 7.44 (s, 1H) 6.90-7.24 (m, 4H) 4.39-4.60 (m, 1H) 3.21-3.32 (m, 1H) 2.53 (s, 3H) 2.21 (s, 3H) 1.45 (s, 6H) 1.38 (s, 3H) 1.16-2.37 (m, 4H), The relative stereochemistry syn was confirmed by dipolar correlations between CH3(8) and CH(5). HPLC: Rt 5.48 min. MS: m/z 625 [M+H]+.

1. customThe solvent was evaporated
2. customthe residue was purified by flash chromatography on silica gel (Companion system; eluent: from 99:1 Dichloromethane/MeOH to 95:5 Dichloromethane/MeOH; 12 g cartridge)