反应详情

温度

6 °C

0.67 cm3 of distilled crotonyl chloride is added to 50 mg of 6-chloro-1H-indazole-3-amine dissolved in 5 cm3 of pyridine and cooled to about 6° C. The mixture is stirred for 10 minutes and the temperature is then allowed to rise to about 19° C. over 22 hours. The reaction medium is then concentrated to dryness under reduced pressure (2 kPa; 40° C.) and the residue is then taken up in 50 cm3 of tetrahydrofuran and 25 cm3 of ethyl acetate. The organic phase is washed with 2×50 cm3 of distilled water and then with 50 cm3 of saturated aqueous sodium chloride solution. The resulting solution is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under the conditions described previously. The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume) and collecting 20 cm3 fractions. The fractions containing the expected product are combined and then evaporated under the conditions already described. After drying (90 Pa; 45° C.), 100 mg of N-(6-chloro-1H-indazol-3-yl)-2-butenamide, E form, are obtained in the form of a white solid melting at 226° C.

1. waitto rise to about 19° C. over 22 hours
2. concentrationThe reaction medium is then concentrated to dryness under reduced pressure (2 kPa; 40° C.)
3. washThe organic phase is washed with 2×50 cm3 of distilled water
4. dry with materialThe resulting solution is dried over magnesium sulphate
5. filtrationfiltered through a sinter funnel
6. customevaporated under the conditions
7. customThe residue obtained
8. customis purified by chromatography under an argon pressure of 50 kPa
9. washon a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
10. customcollecting 20 cm3 fractions
11. additionThe fractions containing the expected product
12. customevaporated under the conditions
13. dry with materialAfter drying (90 Pa; 45° C.), 100 mg of N-(6-chloro-1H-indazol-3-yl)-2-butenamide, E form