Diisopropylethylamine → 6-(3-Hydroxy-3-methylazetidin-1-yl)-5-(1H-imidazol-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

DIPEA (0.139 mL, 0.794 mmol) was added to a mixture of 6-chloro-5-(1H-imidazol-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 69.1, 76 mg, 0.199 mmol) and 3-methylazetidin-3-ol HCl (27 mg, 0.218 mmol) in iPrOH (1 mL) and the RM was stirred at 140° C. 4.5 h. The solvent was evaporated off under reduced pressure and the residue was treated with water, extracted with EtOAc and the combined extracts were washed with water and brine, dried over MgSO4/charcoal and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 15 g, EtOAc/EtOH from 95:5 to 9:1) and crystallized from n-hexane/EtOAc to give the title product as white crystals. UPLC-MS (Condition 3) tR=0.7 min, m/z=434.2 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 1.32 (s, 3H) 3.54-3.67 (m, 4H) 5.47 (s, 1H) 7.05 (s, 1H) 7.26 (s, 1H) 7.35 (d, J=8.66 Hz, 2H) 7.87 (d, J=9.03 Hz, 2H) 8.15 (d, J=2.07 Hz, 1H) 8.76 (d, J=2.07 Hz, 1H) 10.25 (s, 1H) 12.39 (br. s, 1H).

Provenance & Evidence