Acetyl chloride → HCID 44177714, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 11, 50 mg, 0.09 mmol) in DMF (1.0 mL), NaH (60%, 5 mg, 0.13 mmol) was added at room temperature. The resulting brown reaction mixture was allowed to stir for 20 min, cooled down to −25° C. and acetyl chloride (7 μL, 7.7 mg, 0.1 mmol) was added. The reaction mixture was then allowed to warm up to room temperature over 1 h and poured over ice-cold saturated NaHCO3 solution to give a brown precipitate which was collected and purified by reverse phase HPLC. The purified material was triturated with ethyl ether to provide 5-acetyl-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 20) as its bistrifluoroacetate salt as a white solid (31%). 1H NMR (CD3OD, 300 MHz) 8.73 (d, J=1.7 Hz, 1H), 8.70 (dd, J=5.1, 1.5 Hz, 1H), 8.14 (d, J=8.8 Hz, 1H), 8.07 (dt, J=7.4, 1.7 Hz, 1H), 7.97 (s, 1H), 7.87-7.79 (m, 5H), 7.61 (dd, J=8.0, 5.0 Hz, 1H), 4.69 (s, 2H), 4.53 (s, 2H), 4.45 (s, 2H), 4.26-4.14 (m, 1H), 3.77 (br s, 2H), 3.64-3.52 (m, 4H), 3.28-3.20 (m, 2H), 2.80 (s, 3H), 2.26 (d, J=14.4 Hz, 2H), 1.99 (br s, 2H) ppm; MS (ES) 590 (M+H).

Provenance & Evidence