(R)-3-Pyrrolidinol → (R)-4-(3-Hydroxypyrrolidin-1-yl)-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-fluoro-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.1, 50 mg, 0.131 mmol), (R)-pyrrolidin-3-ol (22.8 mg, 0.262 mmol) and TEA (72.9 μL, 0.523 mmol) in DMSO (98 μL) was stirred at 100° C. overnight. The RM was filtered and the filtrate was purified by preparative SFC (Column Diol, isocratic 30% in 6 min) to yield the title compound as a pale brown solid. UPLC-MS (Condition 1) tR=1.05 min, m/z=450.3 [M+H]+, m/z=448.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.82 (m, 1H) 1.82-1.99 (m, 1H) 2.79 (d, J=10.29 Hz, 1H) 3.06-3.14 (m, 1H) 3.14-3.21 (m, 1H) 3.24-3.33 (m, 1H) 4.24 (br. s, 1H) 4.80-5.00 (m, 1H) 6.98 (d, J=8.78 Hz, 1H) 7.35 (d, J=8.41 Hz, 2H) 7.76-8.02 (m, 5H) 9.17 (s, 1H) 10.18 (s, 1H).

Provenance & Evidence