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, 325 mg, 0.33 mmol) in methylene chloride (15 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (565 μL, 1.13 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) two times. The resulting oil was dissolved in tetrahydrofuran (5 mL) at 25° C. and then treated dropwise with a solution of N-(2-methoxy-ethyl)-pyrazine-2,5-diamine (182 mg, 1.08 mmol) and 2,6-lutidine (137 μL, 1.18 mmol) in tetrahydrofuran (6 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight for 16 h at 25° C. 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 40S, Silica, 2/3 to 1/4 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methoxy-ethylamino)-pyrazin-2-yl]-propionamide (295 mg, 62%) as a white foam: (ES)+-HRMS m/e calcd for C22H29ClN4O4S (M+H)+ 481.1671, found 481.1678.

1. concentrationconcentrated in vacuo
2. customazeotroped with methylene chloride (2 mL) two times
3. dissolutionThe resulting oil was dissolved in tetrahydrofuran (5 mL) at 25° C.
4. stirringThe resulting cloudy solution was then stirred overnight for 16 h at 25° C
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