反应详情

To a suspension of 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate (0.451 g, 1.0 mL) in dry tetrahydrofuran (8 mL), 1.0N LiAlH4 in tetrahydrofuran (2.5 mL, 2.5 mmol) was added dropwise at such a rate as to maintain reflux over 15 minutes. Upon the addition, the suspension became a clear light yellow solution, which was kept boiling for an additional 1.5 hours. Excess LiAlH4 was decomposed by cautious addition of a solution of KOH (0.5611 g, 10.0 mmol) in water (3.5 mL). Upon hydrolysis, a white salt precipitated. After the addition was completed, the mixture was heated to reflux for 1 hour. The hot solution was filtered by suction through a buchner funnel. Any remaining product was extracted from the precipitate by refluxing with tetrahydrofuran (10 mL) for 1 hour, followed again by suction filtration. The combined filtrates were concentrated under reduced pressure to give a crude residue, which was then diluted with ethyl acetate and washed with water and brine. The organic layer was dried over MgSO4. After filtration, the solvent was removed under reduced pressure, and a crude product was obtained. The desired product 1-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-4-methylpiperazine (0.1509 g, 50.1%) was obtained by chromatography (silica gel, 70:30:1 methanol/ethyl acetate/NH4OH). Anal. Calc'd for C20H22N5F.0.6H2O: C, 66.32; H, 6.46; N, 19.33; Found: C, 66.31; H, 5.96; N, 18.83. MS (MH+): 352 (base peak).

1. additionwas added dropwise at such a rate as
2. temperatureto maintain
3. temperaturereflux over 15 minutes
4. additionUpon the addition
5. customUpon hydrolysis
6. customa white salt precipitated
7. additionAfter the addition
8. temperaturethe mixture was heated
9. temperatureto reflux for 1 hour
10. filtrationThe hot solution was filtered by suction through a buchner funnel
11. extractionAny remaining product was extracted from the precipitate
12. temperatureby refluxing with tetrahydrofuran (10 mL) for 1 hour
13. filtrationfollowed again by suction filtration
14. concentrationThe combined filtrates were concentrated under reduced pressure
15. customto give a crude residue, which
16. washwashed with water and brine
17. dry with materialThe organic layer was dried over MgSO4
18. filtrationAfter filtration
19. customthe solvent was removed under reduced pressure
20. customa crude product was obtained