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

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Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2, 500 mg, 1.264 mmol, (3S,4S)-pyrrolidine-3,4-diol (157 mg, 1.517 mmol), DIPEA (442 μL, 2.53 mmol) and iPrOH (1.264 mL) were added to a MW vial, which was sealed and subjected to MW irradiation for 30 min at 140° C. The solvent was evaporated off under reduced pressure to give a residue which was treated with 0.5 M HCl (10 mL) and extracted with EtOAc. The combined extracts were washed with HCl 0.5 M and brine, diluted with MeOH (20 mL), dried over MgSO4 and the solvent was evaporated off under reduced pressure and the product was crystallized from EtOAc/MeOH afforded the title compound as a white solid. UPLC-MS (condition 1) tR=2.48 min, m/z=462.0/464.0 [M+H]+, m/z=460.0/462.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.56 (d, J=11.25 Hz, 2H) 3.94-4.06 (m, 4H) 4.79 (br. s, 2H) 7.34 (d, J=8.80 Hz, 2H) 7.88 (d, J=9.05 Hz, 2H) 8.38 (d, J=1.96 Hz, 1H) 8.71 (d, J=1.96 Hz, 1H) 10.34 (s, 1H).

Provenance & Evidence