反应详情

温度

66 °C

8.2 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 570 mg of N-[6-(3-thiophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 20 cm3 of tetrahydrofuran. The reaction medium is heated at about 66° C. for 18 hours. The heating is then stopped and 75 cm3 of ethyl acetate are added. This mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50° 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 2.5 cm), eluting with cyclohexane/ethyl acetate (60/40 by volume) and collecting 20 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 2×5 cm3 of diisopropyl ether. This mixture is filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 40° C.) to give, after drying (90 Pa; 50° C.), 260 mg of N-[6-(3-thiophenyl)-1H-indazol-3-yl] butanamide in the form of a white solid melting at about 198° C.

1. washThis mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution
2. dry with materialThe organic phase is dried over magnesium sulphate
3. filtrationfiltered through a sinter funnel
4. customevaporated under reduced pressure (2 kPa; 50° C.)
5. customThe residue is purified by chromatography under an argon pressure of 50 kPa
6. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with cyclohexane/ethyl acetate (60/40 by volume)
7. customcollecting 20 cm3 fractions
8. additionThe fractions containing the expected product
9. customevaporated under reduced pressure (2 kPa; 50° C.)
10. filtrationThis mixture is filtered through a sinter funnel
11. customevaporated under reduced pressure (2 kPa; 40° C.)
12. customto give
13. dry with materialafter drying (90 Pa; 50° C.), 260 mg of N-[6-(3-thiophenyl)-1H-indazol-3-yl] butanamide in the form of a white solid melting at about 198° C.