反应详情

温度

50 °C

0.95 cm3 of 1N sodium hydroxide is added to 280 mg of ethyl (2E) 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate, described in Example 2, in 25 cm3 of ethanol. The reaction medium is then heated at 50° C. for two hours, followed by addition of a further 1 equivalent of 1N sodium hydroxide. The temperature is maintained at 50° C. for a further 30 minutes and the heating is then stopped. At about 20° C., the medium is neutralized with 1N hydrochloric acid and then concentrated under reduced pressure (2 kPa; 40° C.). The solid thus obtained is taken up in 25 cm3 of tetrahydrofuran, 50 cm3 of ethyl acetate and 25 cm3 of distilled water. The organic phase is washed with 30 cm3 of saturated aqueous sodium chloride solution and then dried over magnesium sulphate. The solution is filtered and evaporated under the conditions described previously. The residue is taken up in 10 cm3 of ethyl acetate and the insoluble material is then filtered off and rinsed with 5 cm3 of ethyl acetate and with 10 cm3 of diethyl ether and dried under reduced pressure (90 Pa; 50° C.). 155 mg of 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoic acid (E form) are obtained in the form of a pale yellow solid melting at 260° C.

1. temperatureThe temperature is maintained at 50° C. for a further 30 minutes
2. customAt about 20° C.
3. concentrationconcentrated under reduced pressure (2 kPa; 40° C.)
4. customThe solid thus obtained
5. washThe organic phase is washed with 30 cm3 of saturated aqueous sodium chloride solution
6. dry with materialdried over magnesium sulphate
7. filtrationThe solution is filtered
8. customevaporated under the conditions
9. filtrationthe insoluble material is then filtered off
10. washrinsed with 5 cm3 of ethyl acetate and with 10 cm3 of diethyl ether
11. customdried under reduced pressure (90 Pa; 50° C.)