反应详情

0.45 g of 2-amino-5-bromopyridine is added to 1.0 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, prepared in Example 56, in 50 cm3 of dioxane, 142 mg of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium, dichloromethane and 646 mg of sodium carbonate in 10 cm3 of water are added to the pale yellow solution, and the mixture is refluxed for 2 hours. The reaction medium is diluted with 50 cm3 of ethyl acetate and 50 cm3 of water, and then filtered through a sinter funnel packed with Celite. The filtrate is separated by settling and the aqueous phase is washed with 2×50 cm3 of saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The crude product obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate gradient mixture (70/30 to 50/50 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.) to give 0.53 mg of N-[6-(6-amino-pyrid-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a solid melting at 138° C.

1. temperaturethe mixture is refluxed for 2 hours
2. filtrationfiltered through a sinter funnel
3. customThe filtrate is separated
4. washthe aqueous phase is washed with 2×50 cm3 of saturated sodium chloride solution
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
8. customThe crude product obtained
9. customis purified by chromatography under an argon pressure of 50 kPa
10. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate gradient mixture (70/30 to 50/50 by volume)
11. additionThe fractions containing the expected product
12. customevaporated under reduced pressure (2 kPa; 50° C.)