反应详情

温度

25 °C

A solution of (E)-3-cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-acrylic acid (158 mg, 0.5 mmol) in fluorobenzene (1 mL) and N,N-dimethylformamide (2 μL) at 25° C. was treated dropwise with oxalyl chloride (54 μL, 0.6 mmol) over 2-3 min. The clear solution was stirred for 1 h at 25° C. and then treated with methyl urea (11 mg, 1.5 mmol). The resulting suspension was heated at 70° C. (bath temperature) for 10 min and then treated with pyridine (81 μL, 1 mmol). The reaction mixture was then stirred at 70° C. for 20 h. The reaction mixture was then cooled to 25° C. and diluted with ethyl acetate (30 mL) and a 3N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 hexanes/ethyl acetate) afforded the (E)-1-{3-cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-acryloyl}-3-methyl-urea (41 mg, 22%) as a white solid: mp 186-192° C.; EI-HRMS m/e calcd for C18H21FN6O2 (M+) 372.1710, found 372.1708.

1. temperatureThe resulting suspension was heated at 70° C. (bath temperature) for 10 min
2. stirringThe reaction mixture was then stirred at 70° C. for 20 h
3. temperatureThe reaction mixture was then cooled to 25° C.
4. customThe two layers were separated
5. extractionthe aqueous layer was extracted with ethyl acetate (1×20 mL)
6. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
7. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo