4-Methylmorpholine → Tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate

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Reaction Steps

To a mixture of 4-(tert-butoxycarbonyl(2,4-dimethoxybenzyl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylic acid (example 1H, 0.89 g, 1.747 mmol) in acetonitrile (17.47 mL) was added dicyclopropylamine hydrochloride (0.303 g, 2.271 mmol), N-methylmorpholine (0.499 mL, 4.54 mmol), DMAP (0.021 g, 0.175 mmol), and HATU (0.797 g, 2.096 mmol). The reaction mixture was stirred at rt 5 h and heated to 50° C. for 45 min. The reaction was cooled to room temperature. Acetonitrile was removed in vacuo and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was purified by flash chromatography using an Isco 80 g column eluting with 1-4% MeOH/CH2Cl2 to yield tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (0.8 g, 78% yield) as an off-white solid.

Provenance & Evidence