Formaldehyde → 1-Ethyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

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Reaction Steps

To a stirred mixture of piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #1A) (0.28 g, 0.86 mmol) and 33% formalin solution (0.045 ml) in 10 ml of AcN:MeOH:H2O (2:1:1) at 0° C. was added NaCNBH3 (0.13 g, 2.1 mmol). The reaction mixture was stirred at room temperature for 30 minand extracted with ethyl acetate (3×20 ml). The organic layers were separated, combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA) to afford 1-ethyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #2A) (0.195 g, 66%) as a white solid.

Provenance & Evidence