反应详情

温度

100 °C

645 mg of 3,4-difluorophenylboronic acid, 1.24 g of caesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl are added to 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously in Example 25, in 30 cm3 of dioxane. The mixture is then heated at about 100° C. for 17 hours. The mixture is allowed to return to about 19° C. and then filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 75 cm3 of ethyl acetate and 50 cm3 of distilled water. The insoluble material is filtered off on a sinter funnel The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure under the conditions described previously. The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume) and collecting 35 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 1.1 g of N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of an orange-coloured oil.

1. customto return to about 19° C.
2. filtrationfiltered through a sinter funnel
3. customevaporated under reduced pressure (2 kPa; 50° C.)
4. filtrationThe insoluble material is filtered off on a sinter funnel The organic phase
5. dry with materialis dried over magnesium sulphate
6. filtrationfiltered through a sinter funnel
7. customevaporated under reduced pressure under the conditions
8. customThe residue is purified by chromatography under an argon pressure of 50 kPa
9. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
10. customcollecting 35 cm3 fractions
11. additionThe fractions containing the expected product
12. customevaporated under reduced pressure (2 kPa; 50° C.)