反应详情

温度

0 °C

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 40 mg, 0.12 mmol) in methylene chloride (2 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (70 μL, 1.40 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min, concentrated in vacuo, and azeotroped with methylene chloride (2 mL) three times. The resulting oil was dissolved in tetrahydrofuran (1 mL) at 25° C. and then treated dropwise with a solution of 5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamine (24 mg, 0.13 mmol) and 2,6-lutidine (17 μL, 0.15 mmol) in tetrahydrofuran (1.5 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight at 25° C. for 16 h. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 4/1 to 7/3 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-yl]-propionamide (25 mg, 42%) as a white foam: (ES)+-HRMS m/e calcd for C24H28ClN3O4S (M+H)+ 490.1562, found 490.1562.

1. concentrationconcentrated in vacuo
2. customazeotroped with methylene chloride (2 mL) three times
3. dissolutionThe resulting oil was dissolved in tetrahydrofuran (1 mL) at 25° C.
4. stirringThe resulting cloudy solution was then stirred overnight at 25° C. for 16 h
5. extractionextracted with methylene chloride (3×25 mL)
6. dry with materialThe combined organic layers were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo