2-Methoxypropene → 2,2-dimethyl-1-(1-methylethyl)-6-(pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[(1-methylethyl)amino]-5-(pyridin-4-yl)thiophene-2-carboxylic acid (0.225 g, 0.858 mmol), ammonium chloride (0.459 g, 8.58 mmol) and triethylamine (1.21 mL, 8.58 mmol) in DMF (5 mL) was stirred at room temperature for 15 min. To the resulting mixture was added 1-(3-(dimethylamino)propyl)-3-ethyl carbodiimide hydrochloride (0.493 g, 2.57 mmol), and 1-hydroxybenzotriazole (0.347 g, 2.57 mmol) and the reaction was stirred at room temperature for 65 h. Then, the reaction mixture was diluted with sat. NaHCO3 (120 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with water (2×50 mL) and brine (100 mL), dried over magnesium sulfate, filtered and concentrated to give crude 3-[(1-methylethyl)amino]-5-(pyridin-4-yl)thiophene-2-carboxamide (0.225 g) as an orange solid. A mixture of 3-[(1-methylethyl)amino]-5-(pyridin-4-yl)thiophene-2-carboxamide (0.105 g) and 2-methoxypropene (1.53 mL, 16.0 mmol) in acetic acid (1.5 mL) was heated at 35° C. overnight. Then, the reaction mixture was cooled to room temperature and concentrated. The obtained residue was dissolved in methanol (10 mL), and the solution was concentrated with NaHCO3 (1 g) and silica gel (5 mL), and the residue was purified by flash chromatography (Combiflash, silica gel, ethyl acetate to 95:5 ethyl acetate /methanol) to give the title compound (0.063 g, 2 step yield 52%) as an orange solid:

Provenance & Evidence