反应详情

温度

0 °C

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-propionic acid (prepared as in Example 45, 1.05 g, 3.04 mmol) and N,N-dimethylformamide (5 drops) in methylene chloride (10 mL) cooled to 0° C. was treated with oxalyl chloride (0.39 mL, 4.57 mmol). The reaction mixture was stirred at 0° C. for 1 h and then at 25° C. for 1 h. The solution was then concentrated in vacuo, and the orange-brown gel was dissolved in methylene chloride (5 mL). The resulting solution was added dropwise via an addition funnel at 0° C. to a solution of 2-amino-5-bromopyrazine (0.79 g, 4.57 mmol, prepared according to Tetrahedron 1988, 44, 2977–2983) in methylene chloride (5 mL) and pyridine (0.37 mL, 4.57 mmol). The reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 3 h. The reaction mixture was quenched with a 1N aqueous citric acid solution (10 mL) and stirred for 15 min. The reaction was then diluted with a 1N aqueous citric acid solution (50 mL) and ethyl acetate (75 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL), and a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 50% ethyl acetate/hexanes) afforded N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-propionamide (0.622 g, 41%) as a yellow-orange foam: mp 97–103° C. (foam to gel); (ES)+-HRMS m/e calcd for C19H19BrClN3O4S (M+H)+ 500.0041 found 500.0048.

1. waitat 25° C. for 1 h
2. concentrationThe solution was then concentrated in vacuo
3. dissolutionthe orange-brown gel was dissolved in methylene chloride (5 mL)
4. stirringThe reaction mixture was stirred at 0° C. for 30 min
5. waitat 25° C. for 3 h
6. customThe reaction mixture was quenched with a 1N aqueous citric acid solution (10 mL)
7. stirringstirred for 15 min
8. additionThe reaction was then diluted with a 1N aqueous citric acid solution (50 mL) and ethyl acetate (75 mL)
9. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL)
10. dry with materiala saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo