Thiophene-3-carboxylic acid → HCID 11949929, compound

Participants

Reaction Steps

The compounds 5-(5-amino-2-methylphenyl)-1-(2,6-difluorophenyl)-7-(methylthio)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (0.205 g, 0.5 mmol), 3-thiophenecarboxylic acid (0.0647 g, 0.5 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.107 g, 0.55 mmol), 4-(dimethylamino)pyridine (0.002 g, 0.016 mmol), and triethylamine (0.14 mL, 1 mmol), were dissolved in chloroform (10 mL) and stirred under argon at room temperature for 16 h. The reaction was not complete. An additional 3-thiophenecarboxylic acid (0.13 g, 1.0 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.107 g, 0.55 mmol) were dded and heated to 40° C. for 17 h. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water (3×), brine (1×), dried over anhydrous Na2SO4, filtered and evaporated. The crude product was flash chromatographed on silica gel (10 g) eluted with 0-5% MeOH/CH2Cl2 to give the title compound as a solid. LC-MS m/z 524 (M+H)+, 2.2 min (ret. time).

Provenance & Evidence