Potassium Carbonate → 2-(7-(Dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)thiazole-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (1J, 300 mg, 0.89 mmol) and benzoyl isothiocyanate (0.16 ml, 1.15 mmol) in acetone (4 ml) were stirred at rt for 1.5 h. The solvent was removed in vacuo and the residue taken up in EtOH (6 ml). K2CO3 (172 mg, 1.241 mmol) was added and the reaction heated at 60° C. for 3 h. The reaction was cooled to rt and ethyl 3-bromo-2-oxopropanoate (692 mg, 3.55 mmol) was added. The reaction was heated at 70° C. overnight. Upon completion of the cyclization step, 1N NaOH (6.3 ml, 6.30 mmol) was added to the reaction mixture and heated at 60° C. for 4 h. The reaction was cooled to room temperature and the solvent removed in vacuo. The remaining aqueous solution was acidified to pH 1 and the precipitate removed by vacuum filtration, washing with water, EtOAc, and then dichloromethane to afford 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-4-ylamino)thiazole-4-carboxylic acid (325 mg, 79% yield) as brown solid.

Provenance & Evidence