反应详情

A mixture of 4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzoic acid (1.05 g) and dry tetrahydrofuran (30 ml) was stirred at ambient temperature whilst triethylamine (1.1 ml) was added. The mixture was stirred at ambient temperature for 0.5 h then cooled to 3° C. and methyl chloroformate (1.2 ml) was added dropwise over 5 to 10 minutes at 3-9° C. The mixture was stirred for 1 hour at 3-9° C. and then added to concentrated aqueous ammonia solution (70 ml, SG 0.880) with rapid stirring. The mixture was stirred for 2 hours at 5° C. and allowed to warm up to ambient temperature. The mixture was concentrated under reduced pressure and then treated with 1M sodium hydroxide solution (200 ml). The mixture was stirred for 0.5 hour and then filtered. The solid obtained was stirred with 2M sodium hydroxide solution (50 ml) for 6 hours and then allowed to stand at ambient temperature for 18 hours. The mixture was filtered to give a solid which was washed with water and dried. This solid was purified by flash column chromatography on silica using dichloromethane/industrial methylated spirit/triethylamine (25:2.5:1.5) as the mobile phase. The appropriate fractions were combined and concentrated to give a residue which was washed with water and dried under vacuum at 40° C. to give 4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzamide, m.p. 290-293° C.

1. additionwas added
2. temperaturethen cooled to 3° C.
3. stirringThe mixture was stirred for 1 hour at 3-9° C.
4. stirringThe mixture was stirred for 2 hours at 5° C.
5. temperatureto warm up to ambient temperature
6. concentrationThe mixture was concentrated under reduced pressure
7. additiontreated with 1M sodium hydroxide solution (200 ml)
8. stirringThe mixture was stirred for 0.5 hour
9. filtrationfiltered
10. customThe solid obtained
11. waitto stand at ambient temperature for 18 hours
12. filtrationThe mixture was filtered
13. customto give a solid which
14. washwas washed with water
15. customdried
16. customThis solid was purified by flash column chromatography on silica
17. concentrationconcentrated
18. customto give a residue which
19. washwas washed with water
20. customdried under vacuum at 40° C.