反应详情

14 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1.1 g of N-[6-chloro-5-(4-ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 50 cm3 of tetrahydrofuran. The medium is then refluxed for 18 hours and the mixture is then allowed to return to room temperature and 75 cm3 of ethyl acetate are added; the organic phase is washed with 2×100 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 75 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure (2 kPa; 45° C.). 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 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); the residue is taken up in 20 cm3 of diisopropyl ether, filtered off on a sinter funnel and washed with 2×10 cm3 of diisopropyl ether. After drying under reduced pressure (90 Pa; 50° C.), 440 mg of N-(6-chloro-5-phenyl-1H-indazol-3-yl)butanamide are obtained in the form of white crystals melting at 240° C.

1. temperatureThe medium is then refluxed for 18 hours
2. customto return to room temperature
3. washthe organic phase is washed with 2×100 cm3 of saturated aqueous sodium hydrogen carbonate solution
4. customThe organic phase is separated out
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. customevaporated to dryness under reduced pressure (2 kPa; 45° C.)
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 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume)
10. additionThe fractions containing the expected product
11. customevaporated under reduced pressure (2 kPa; 50° C.)
12. filtrationfiltered off on a sinter funnel
13. washwashed with 2×10 cm3 of diisopropyl ether
14. dry with materialAfter drying under reduced pressure (90 Pa; 50° C.), 440 mg of N-(6-chloro-5-phenyl-1H-indazol-3-yl)butanamide