反应详情

Bismuth chloride (347 mg, 1.1 mmol) was added to a mixture of [2-(trifluoromethyl)-2-oxiranyl]methyl 4-methylbenzenesulfonate (3.41 g, 11.5 mmol) and 6-methyl-1-phenyl-1H-indazol-4-amine (2.45 g, 1.1 mmol) in dry dichloromethane (4.5 ml) and the mixture stirred at room temperature under nitrogen over the weekend. More bismuth chloride (173 mg, 0.55 mmol) and dichloromethane (0.5 ml) were then added and the mixture stirred overnight and then diluted with chloroform (50 ml) and dry tetrahydrofuran (25 ml). N,N-Diisopropylethylamine (0.38 ml, 2.2 mmol) was added followed by polymer supported carbonate resin (Fluka, ca. 3.5 mmoles carbonate/g resin, 9.4 g) and 4 A molecular sieves. After 6 hours LCMS indicated the reaction to be complete and the mixture was filtered. The filtrate was washed with water, the aqueous phase was back-extracted with dichloromethane and the combined organic phases were dried and evaporated to give crude product which was purified by silica gel chromatography using the Flashmaster II (100 g cartridge) eluting with a 0 to 100% cyclohexane:ethyl acetate gradient. Product containing fractions were combined with similar fractions from a parallel reaction (1.28 g input of Intermediate 9) to give the title compound (2.67 g).

1. stirringthe mixture stirred overnight
2. customthe reaction
3. filtrationthe mixture was filtered
4. washThe filtrate was washed with water
5. extractionthe aqueous phase was back-extracted with dichloromethane
6. customthe combined organic phases were dried
7. customevaporated
8. customto give crude product which
9. customwas purified by silica gel chromatography
10. washeluting with a 0 to 100% cyclohexane
11. additionProduct containing fractions
12. customwere combined with similar fractions from a parallel reaction (1.28 g input of Intermediate 9)