反应详情

A solution of 2-chloro-6-fluorobenzoyl chloride (0.169 g) in dry tetrahydrofuran (1 ml) was added to a stirred mixture of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (0.289 g) and diisopropylethylamine (0.21 ml) in a mixture of dichloromethane (4 ml) and tetrahydrofuran (3 ml) cooled to <5° C. After the addition, the cooling bath was removed and the reaction mixture stirred at room temperature for 20 minutes. Water (10 ml) and dichloromethane (10 ml) were added to the reaction mixture and the resultant mixture stirred vigorously. The phases were separated using a hydrophobic frit and the aqueous phase washed with additional dichloromethane (10 ml). The organic phase was evaporated and the residue purified by chromatography on silica (20 g cartridge) eluting with 0-100% ethyl acetate in cyclohexane. Appropriate fractions were combined and evaporated to give the title compound (0.409 g).

1. temperaturecooled to <5° C
2. additionAfter the addition
3. customthe cooling bath was removed
4. additionWater (10 ml) and dichloromethane (10 ml) were added to the reaction mixture
5. stirringthe resultant mixture stirred vigorously
6. customThe phases were separated
7. washthe aqueous phase washed with additional dichloromethane (10 ml)
8. customThe organic phase was evaporated
9. customthe residue purified by chromatography on silica (20 g cartridge)
10. washeluting with 0-100% ethyl acetate in cyclohexane
11. customevaporated