反应详情

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (202 mg, 0.5 mmol), 3,5-difluorophenylboronic acid (156 mg, 1.0 mmol), copper (II) acetate (182 mg, 1.0 mmol), triethylamine (252 mg, 2.5 mmol) and freshly activated 4 Å molecular sieves (1.5 g) in DCM (10 mL) was stirred at ambient temperature and under ambient atmosphere for 64 hours. The reaction mixture was filtered, washed with DCM (2×10 mL), evaporated in vacuo and the residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL). The ethyl acetate layer was separated, washed sequentially with aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase using 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA) as eluant to give the title compound (45 mg).

1. filtrationThe reaction mixture was filtered
2. washwashed with DCM (2×10 mL)
3. customevaporated in vacuo
4. customthe residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL)
5. customThe ethyl acetate layer was separated
6. washwashed sequentially with aqueous sodium hydrogen carbonate solution and brine
7. dry with materialdried (MgSO4)
8. customevaporated to a residue which
9. customwas chromatographed by preparative HPLC on C18 reversed phase