反应详情

A solution of 3-hydroxy-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.66 mmol), N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (239 mg, 0.66 mmol) and potassium carbonate (181 mg, 1.31 mmol) in DMA (3 mL) was heated in a microwave reactor at 160° C. for 6 hours. Water (20 mL) was added and the reaction mixture extracted with ethyl acetate. The organic layer was washed with brine (20 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 2% methanol in ethyl acetate, and then chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product (542 mg).

1. extractionthe reaction mixture extracted with ethyl acetate
2. washThe organic layer was washed with brine (20 mL)
3. dry with materialdried (MgSO4)
4. customevaporated to a residue which
5. customwas chromatographed on silica
6. washeluting with 2% methanol in ethyl acetate
7. customchromatographed by preparative HPLC on C18 reversed phase
8. washeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)