Acetic Acid → 1-tert-Butyloxycarbonyl-4-[N-methyl-N-(3-cyclopropylmethylamino-2-pyridinyl)amino]piperidine

Participants

Reaction Steps

1-tert-Butyloxycarbonyl-4-[N-methyl-N-(3-amino-2-pyridinyl)amino]piperidine (1.64 g, 5.37 mmol) is dissolved in methanol (0.2M) and cooled to 0°. Cyclopropylcarboxaldehyde (0.40 ml, 5.37 mmol) is added. After stirring 5 min, sodium cyanoborohydride (337 mg, 5.37 mmol) is added. The reaction is refluxed one hour, then stirred overnight at 20°-25°. Acetic acid (53.7 mmol) is added and the reaction refluxed 3 hr. After cooling to 20°-25°, cyclopropylcarboxaldehyde (820 mg, 2.68 mmol) and sodium cyanoborohydride (168 mg 2.68 mmol) are added and the reaction stirred 16 hr at 20°-25°. The mixture is diluted with water, adjusted to pH 9 with sodium hydroxide (1N) and extracted with chloroform. The extract is filtered and concentrated. The concentrate is chromatographed (silica gel; ethyl acetate/hexane (20/80) to give the title compound; NMR (300 MHz, CD3OD) 7.39, 6.79, 3.79, 3.07, 2.80, 2.63, 2.44, 1.52, 1.33, 1.27, 0.93, 0.35 and 0.05δ.

Provenance & Evidence