Hydrochloric Acid → 5-bromo-6-(pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 1 g, 2.53 mmol) and pyrrolidine (0.544 g, 5.06 mmol) were suspended in iPrOH (2.53 mL), and DIPEA (1.325 mL, 7.58 mmol) was added. The RM was subjected to MW irradiation at 140° C. for 1 hr. The RM was treated with 0.5 M HCl (40 mL) and extracted with EtOAc. The combined extracts were sequentially washed with 0.5 M HCl (40 mL) and brine, dried over Na2SO4 and evaporated to dryness under reduced pressure. Crystallization from a cyclohexane/EtOAc mixture yielded the title compound as an off-white solid. UPLC-MS (Condition 3) tR=1.34 min, m/z=430.1/432.1 [M+H]+, m/z=428.3/430.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.76-2.01 (m, 4H) 3.60-3.80 (m, 4H) 7.33 (d, J=8.20 Hz, 2H) 7.72-7.91 (m, 2H) 8.32 (d, J=1.95 Hz, 1H) 8.66 (d, J=1.95 Hz, 1H) 10.20 (s, 1H).

Provenance & Evidence