Triethylamine → N-[(4-Amino-1-isobutyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methyl]-N-methoxycyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 1-isobutyl-2-[(methoxyamino)methyl]-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine (0.53 g, 1.91 mmol) was dissolved in dichloromethane (19 mL) and cooled to −5° C. Triethylamine (293 uL, 2.10 mmol) was added followed by dropwise addition of cyclopropane carbonyl chloride (173 uL, 1.91 mmol). The solution was allowed to stir at RT for 2 hours, then cooled back to −5° C. More triethylamine (38 uL, 0.27 mmol) and cyclopropane carbonyl chloride (23 uL, 0.25 mmol) were added and the reaction was allowed to stir at 0° C. for 45 minutes. More cyclopropane carbonyl chloride (5 uL, 0.06 mmol) was added and stirring continued for another 30 minutes. Dichloromethane (100 mL) was added and the solution was washed successively with saturated aqueous sodium bicarbonate (30 mL), water (3×25 mL), and brine (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by HPFC eluting with a gradient of 0-35% CMA in chloroform and then recrystallized from ethyl acetate/hexanes to provide 292 mg of pure product as an off-white powder, mp 135.0-137.0° C. Anal. Calcd for C18H27N5O2 C, 62.59; H, 7.88; N, 20.27. Found: C, 62.68; H, 7.82; N, 19.93.

Provenance & Evidence