(-)-2-Aminobutyric acid → Methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-methylthiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl 2-bromo-3-oxobutanoate (213 mg, 1.094 mmol, prepared following the procedure described by Abu T. Khan et al. in Tetrahedron Letters 2006, 47, 2751-2754) was added to a suspension of N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 2B, 290 mg, 0.730 mmol) in ethanol (5 ml) and the reaction mixture was heated at 65° C. for 2 h. LC/MS shows completion of reaction (reaction remained as suspension all the time). The reaction mixture was concentrated to remove ethanol, and taken up in dichloromethane. The solution was washed with saturated sodium bicarbonate and the aqueous layer was back extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude was purified by flash chromatography using an automated ISCO system (40 g column, eluting with 0-5% methanol/dichloromethane) to afford methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-methylthiazole-5-carboxylate (301 mg, 0.610 mmol, 84% yield) as a white solid.

Provenance & Evidence