Diisopropylethylamine → N-(2,2-difluoroethyl)-4-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a slurry of N-(2,2-difluoroethyl)-4-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzamide hydrochloride (0.19 g, 0.51 mmol), DIPEA (0.45 mL, 2.6 mL) and tetrahydrofuran (3 mL) was added 2-(3-fluorophenyl)-4-oxopiperidine-1-carbonyl chloride (reagent preparation 37) (0.13 g, 0.51 mmol). The reaction mixture was heated (50° C.) for 3 h and then concentrated. Purification by preparative reverse phase HPLC provided N-(2,2-difluoroethyl)-4-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzamide (37 mg, 13% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): 7.82 (d, 2H), 7.55 (d, 2H), 7.47 (dd, 1H), 7.20-7.34 (m, 3H), 7.13 (d, 1H), 6.93-7.06 (m, 3H), 6.43 (t, 1H), 5.99 (tt, 1H), 5.34-5.40 (m, 1H), 4.54 (s, 2H), 4.20-4.30 (m, 2H), 3.73-3.93 (m, 5H), 3.20-3.30 (m, 1H), 2.84-3.06 (m, 2H), 2.54-2.64 (m, 1H), 2.32 (d, 1H); MS (EI) for C30H28F3N3O4: 552 (MH+).

Provenance & Evidence