反应详情

A solution of N-[7a-(5-amino-2-fluoro-phenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (705 mg, 1.90 mmol), 5-fluoro-2-chloropyrimidine (1.01 g, 7.61 mmol), and diisopropylethylamine (1.66 mL, 9.52 mmol) are heated in 1,4-dioxane (20 mL) to reflux for 4 hours under nitrogen. The reaction is cooled, diluted with water, and extracted with ethyl acetate (3×). The organic layers are combined, dried over sodium sulfate, filtered and the solvent removed in vacuo to give crude product. The crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient to give the title compound (590 mg, 66%). ES/MS (m/e): 467 (M+H).

1. temperatureto reflux for 4 hours under nitrogen
2. temperatureThe reaction is cooled
3. extractionextracted with ethyl acetate (3×)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customthe solvent removed in vacuo
7. customto give crude product
8. customThe crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient