HCID 53956777, compound → HCID 10347790, compound

Participants

Reaction Steps

2-(R)-(3-(S)-((4-(3,3-Difluoro-3-(4fluorophenyl)propyl) piperidin-1-yl)methyl)-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-(cyclobutyl)propanoic acid benzyl ester (170 mg, 0.261 mmol, from EXAMPLE 155, Step I) dissolved in 95% ethanol (15 mL) was hydrogenated at atmospheric pressure using 20% Pd(OH)2/C (35 mg). After 1 h, the mixture was filtered, the catalyst was washed with 95% ethanol, and the filtrate was evaporated. The crude product was purified by flash column chromatography on silica gel eluting with 95:5:1 v/v/v CH2Cl2/CH3OH/NH4OH followed by 90:10:1 v/v/v CH2Cl2/CH3OH/NH4OH to give the title compound as 137 mg of amorphous glass which could be recrystallized from CH3OH: 1H NMR (500 MHz, CD3OD) δ 7.49 (dd, J=9, 5, 2H), 7.39-7.33 (m, 1H), 7.19-7.11 (m, 4H), 7.01 (td, J=8, 2, 1H), 3.63 (dd, J=11, 8, 1H), 3.57 (bt, J=10, 1H), 3.42 (dd, J=9,4, 1H), 3.39-3.26 (m, 2H), 3.15 (bq, J=10, 1H), 2.89 (d, J=11, 1H), 2.77-2.66 (m, 2H), 2.54-2.44 (m, 2H), 2.35 (dd, J=13, 4, 1H), 2.22-2.06 (m, 4H), 2.03-1.54 (m, 10H), 1.31-1.00 (m, 5H); ESI-MS 561 (M+H); HPLC A: 2.72 min.

Provenance & Evidence