Diisopropylethylamine → N-[4-Cyano-1-(3-ethoxy-4-methyl-benzyl)-piperidin-4-yl]-5-methyl-nicotinamide

Participants

Reaction Steps

To a solution of N-(4-cyano-piperidin-4-yl)-5-methyl-nicotinamide dihydrochloride (171.0 mg, 0.54 mmol, 1.0 equiv) in isopropanol (5 mL) was added 3-ethoxy-4-methyl-benzaldehyde (88.7 mg, 0.54 mmol, 1.0 equiv; intermediate B10), titanium tetra-isopropoxide (766.5 mg, 2.70 mmol, 5.0 equiv) and N-ethyl diisopropylamine (209.5 mg, 1.62 mmol, 3.0 equiv), followed by sodium cyanoborohydride (67.4 mg, 1.08 mmol, 2.0 equiv) after stirring for 1 h. The reaction mixture was allowed to react overnight and then poured directly onto a silica column eluting with ethyl acetate. The isolated crude product was purified by a second silica column eluting with dichloromethane/methanol (93:7) delivered finally 22.0 mg (24%) of the title compound as colorless oil. MS (ISP): 393.2 [M+H]+.

Provenance & Evidence