Acetic Acid → 4-(4-Chloro-benzoylamino)-1-(4-chloro-3-ethoxy-benzyl)-piperidine-4-carboxylic acid amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-chloro-N-(4-cyano-piperidin-4-yl)-benzamide hydrochloride (45.03 mg, 0.15 mmol, 1.0 equiv) in ethanol (1 mL), acetic acid (72.1 mg, 1.2 mmol, 8.0 equiv) and N-ethyl diisopropylamine (77.6 mg, 0.6 mmol, 4.0 equiv) was added 4-chloro-3-ethoxy-benzaldehyde (33.2 mg, 0.18 mmol, 1.2 equiv; intermediate B1) and the mixture stirred at 55° C. After 1 h, sodium cyanoborohydride (47.1 mg, 0.75 mmol, 5.0 equiv), dissolved in ethanol (0.5 mL), was added and the mixture stirred at 55° C. over night. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 9.7 mg (14%) of the title compound. MS (ISP): 450.2 [M+H]+.

Provenance & Evidence