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

Participants

Reaction Conditions

Reaction Steps

Methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate dihydrochloride salt (51.7 mg, 0.13 mmol) was taken into DMF (1 mL) and dichloromethane (1 mL) followed by addition of DIPEA (88 uL, 0.52 mmol) and the mixture was cooled to 0° C. 4-(Fluoromethyl)piperidine-1-carbonyl chloride (reagent preparation 37) (33 mg, 0.13 mmol) was added to the mixture in a minimum of dichloromethane then stirred for 30 minutes. The mixture was partitioned with ethyl acetate and water and the organic phase washed twice with water, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (4:1 ethyl acetate:hexanes) to give methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate (40.3 mg, 66% yield) as a white solid. 1H NMR (400 MHz, d6-DMSO): 7.58 (s, 1H), 7.47 (s, 1H), 7.45-7.42 (m, 2H), 7.31 (dd, 1H), 7.02 (d, 1H), 4.42 (s, 2H), 4.37 (d, 1H), 4.26 (d, 1H), 4.17 (br s, 1H), 3.77 (s, 3H), 3.60 (br m, 4H), 2.75 (tr, 2H), 1.85 (br, 1H), 1.63 (d, 2H), 1.25 (q, 2H). MS (EI) for C25H18FN5O4: 483 (MH+).

Provenance & Evidence