反应详情

温度

0 °C

A solution of 2-(4-methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (50 mg, 0.13 mmol) in methylene chloride (1 mL) was treated with N,N-dimethylformamide (3 drops) and then cooled to 0° C. The reaction mixture was then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.08 mL, 0.156 mmol). The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to 25° C., and then concentrated in vacuo to remove solvents and excess oxalyl chloride. The resulting residue was re-dissolved in dry tetrahydrofuran (1 mL) and was treated dropwise with a solution of 2-aminothiazole (28 mg, 0.27 mmol) in tetrahydrofuran (1 mL) and 2,6-lutidine (0.08 mL, 0.65 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was then diluted with water (50 mL) and extracted with methylene chloride (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 7/3 hexanes/ethyl acetate to 6/4 hexanes/ethyl acetate to 1/1 hexanes/ethyl acetate) afforded 2-(4-methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-N-thiazole-2-yl-propionamide (37 mg, 61%) as a white foam: EI-HRMS m/e calcd for C19H21F3N2O4S2 (M+H)+ 463.0968 found 463.0974.

1. temperatureto warm to 25° C.
2. concentrationconcentrated in vacuo
3. customto remove solvents and excess oxalyl chloride
4. dissolutionThe resulting residue was re-dissolved in dry tetrahydrofuran (1 mL)
5. customThe resulting reaction mixture
6. stirringwas stirred at 25° C. for 16 h
7. extractionextracted with methylene chloride (3×50 mL)
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo