Hydrochloric Acid → 5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)nicotinamide

Participants

Reaction Steps

A suspension of 5-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide (Stage 169.2, 1 g, 2.427 mmol) and (3S,4S)-pyrrolidine-3,4-diol (0.3 g, 2.91 mmol) in a mixture of DIPEA (1.272 mL, 7.28 mmol) and iPrOH (3.24 mL) was subjected to MW irradiation at 140° C. for 1 h. The RM was treated with 0.5 M HCl (40 mL) and extracted with EtOAc. The combined extracts were washed with water, sat. aq. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue that was suspended in a mixture of cyclohexane EtOAc. The resulting solid was filtered-off, washed with cyclohexane and dried to afford the title product as an off-white solid. UPLC-MS (Condition 3) tR=0.98 min, m/z=477.9 [M+H]+, m/z=475.8 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.55 (d, J=11.13 Hz, 2H) 3.91-4.09 (m, 4H) 5.18 (d, J=2.81 Hz, 2H) 7.34 (d, J=9.05 Hz, 2H) 7.80-7.93 (m, 2H) 8.34 (d, J=1.96 Hz, 1H) 8.67 (d, J=1.96 Hz, 1H) 10.24 (s, 1H).

Provenance & Evidence