Trifluoroacetic acid → 1-{[7-{2-[(2-fluoroethyl)amino]-1H-benzimidazol-5-yl}-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-2-(3-fluorophenyl)piperidin-4-one

Participants

Reaction Steps

1,1-Dimethylethyl 7-(2-[(2-fluoroethyl)amino]-1-{[(2-methylpropyl)oxy]carbonyl}-1H-benzimidazol-5-yl)-2,3-dihydro-1,4-benzoxazepine-4 (5H)-carboxylate (59.4 mg, 0.11 mmol) was taken into neat TFA (1 mL) and allowed to stand for 1 h at room temperature then concentrated and dried. The residue was taken into THF (5 mL) followed by addition of DIPEA (0.2 mL, 1.1 mmol) followed by addition of 2-(3-fluorophenyl)-4-oxopiperidine-1-carbonyl chloride (reagent preparation 37) (29 mg, 0.11 mmol) in a minimum of THF and the resulting solution was stirred at room temperature for 30 minutes. The mixture was then concentrated and taken up into methanol (5 mL) followed by addition of solid potassium carbonate (80 mg, 0.56 mmol) and stirring was continued for 30 minutes. The mixture was then concentrated and partitioned with ethyl acetate and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated. The residue thus obtained was triturated with ethyl ether and the solid collected by filtration and dried to afford 1-{[7-{2-[(2-fluoroethyl)amino]-1H-benzimidazol-5-yl}-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-2-(3-fluorophenyl)piperidin-4-one (46.4 mg, 75% yield). 1H NMR (400 MHz, d6-DMSO): 7.51 (s, 1H), 7.42 (d, 1H), 7.36 (s, 1H), 7.31 (q, 1H), 7.18 (d, 1H), 7.12-7.03 (m, 4H), 6.99 (d, 1H), 5.20 (tr, 1H), 4.66 (tr, 1H), 4.57 (dd AB, 2H), 4.54 (tr, 1H), 4.20 (br m, 2H), 3.75-3.56 (br m, 6H), 2.86 (m, 2H), 2.60 (m, 1H), 2.33 (br d, 1H). MS (EI) for C30H29F2N5O3: 547 (MH+).

Provenance & Evidence