Methanol → 4-Amino-3-pyridinecarboxamide

Participants

Reaction Conditions

Reaction Steps

4-tert-Butoxycarbonylamino-nicotinic acid (1.0 g, 4.20 mmol) was suspended in dry DMF (50 mL) followed by carbonyl-diimidazole (CDI, 1.36 g, 8.40 mmol). The mixture was heated to 60° C. for 1 h, then cooled. Dry ammonia gas was slowly bubbled through this solution for 1 h, followed by evaporation of the mixture. The residue was dissolved in water (20 mL)/chloroform (50 mL) and shaken then the layers separated. The aqueous layer was extracted further with chloroform (3×50 mL) and the combined organic extracts dried (MgSO4) and evaporated to give a yellow oily solid. Silica gel chromatography (CH2Cl2, 0–15% MeOH gradient) gave the desired product, (3-Carbamoyl-pyridin-4-yl)-carbamic acid tert-butyl ester, as a yellow solid. This material was directly treated with trifluoroacetic acid (TFA, 20 mL) stirred at r.t. for 45 min., then evaporated to give the desired amine, 4-Amino nicotinamide, as its TFA salt (892 mg, 85% yield over 2 steps).

Provenance & Evidence