Diisopropylethylamine → 2-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate

Participants

Reaction Steps

To a solution 2-methylpropyl 2-[4-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (0.22 g, 0.56 mmol) and diisopropylethylamine (0.50 mL, 2.81 mmol) in dimethylfomamide (10 mL) at 0° C. a solution of 2-(4-fluorophenyl)-4-oxopiperidine-1-carbonyl chloride (reagent preparation 37) (0.15 g, 0.59 mmol) in tetrahydrofuran (5 mL) was added and the reaction mixture was stirred for 2 hours at room temperature. The mixture was diluted with ethyl acetate (250 mL) and partitioned with water (100 mL). The organic layer was separated and washed with water (50 mL), 10% aqueous citric acid (50 mL), brine then dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (hexane-acetone 4:1 to 7:3) provided 2-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (0.28 g, 80%). 1H NMR (400 MHz, d6-DMSO): 7.73 (d, 1H), 7.68-7.61 (m, 4H), 7.62 (d, 1H), 7.54 (dd, 1H), 7.30 (m, 1H), 7.15 (d, 1H), 7.10 (m, 3H), 7.04 (d, 2H), 5.20 (t, 1H), 4.62 (s, 2H), 4.24 (m, 2H), 4.04 (d, 2H), 3.68 (m, 3H), 3.40 (m, 1H), 2.86 (m, 2H), 2.61 (m, 1H), 2.32 (2t, 1H), 1.86 (m, 1H), 0.76 (m, 6H). MS (EI) for C35H35FN4O5: 611 (MH+).

Provenance & Evidence