Hydrochloric Acid → 6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine

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Reaction Conditions

Reaction Steps

To a solution of methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate (example 8) (181 mg, 0.38 mmol, in methanol (6 mL) was added a 2 M aqueous solution of potassium hydroxide (6 mL), and the resulting mixture was stirred at 65° C. overnight. The pH was adjusted to 9 with 1 N aqueous hydrochloric acid, ethyl acetate was added (50 mL), and the organic layer was washed with brine (2×25 mL), dried over sodium sulfate, filtered and concentrated. Purification by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile) provided the title compound as the acetate salt (56 mg, 31% yield) as a colorless solid. 1H NMR (400 MHz, methanol-d4): 7.47 (m, 1H), 7.43 (m, 2H), 7.30 (m, 2H), 7.02 (d, 1H), 4.48 (s, 2H), 4.29 (dd, 2H), 4.19 (m, 2H), 3.71 (m, 4H), 2.85 (m, 2H), 1.95 (s, 3H), 1.87 (m, 1H), 1.72 (m, 2H), 1.36 (m, 2H); MS (EI) for C23H26FN5O2: 424 (MH+).

Provenance & Evidence