反应详情

A 5 mL microwave tube was charged with N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (250 mg, 0.464 mmol) and 3-aminopropionitrile (163 mg, 2.319 mmol) and CsF (70.5 mg, 0.464 mmol) in dimethyl sulfoxide (3.00 mL) to give a yellow solution at rt under nitrogen. The sealed reaction mixture was microwaved at 90° C. for 30 min. For second time, the sealed reaction mixture was microwaved at 100° C. for 1 h. The reaction was diluted with water and a white solid formed. The reaction was filtered and washed with water. The crude product was chromatographed on silica gel column and eluted with CH2Cl2 with chloroform/methanol/ammonium hydroxide (90:9:1) (5% to 100%) and collected fractions. Water and DCM were added to solid and take to a pH=6 and extracted with DCM (3×). The CH2Cl2 layers were dried over Na2SO4, filtered, and concentrated to obtain N-{3-[5-{2-[(2-cyanoethyl)amino]-4-pyrimidinyl}-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (35 mg, 12%). MS (ESI): 573 [M+H]+.

1. customto give a yellow solution at rt under nitrogen
2. customThe sealed reaction mixture
3. customwas microwaved at 90° C. for 30 min
4. customFor second time, the sealed reaction mixture
5. customwas microwaved at 100° C. for 1 h
6. customa white solid formed
7. filtrationThe reaction was filtered
8. washwashed with water
9. customThe crude product was chromatographed on silica gel column
10. washeluted with CH2Cl2 with chloroform/methanol/ammonium hydroxide (90:9:1) (5% to 100%)
11. customcollected fractions
12. additionWater and DCM were added to solid
13. extractionextracted with DCM (3×)
14. dry with materialThe CH2Cl2 layers were dried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated