反应详情

温度

24 °C

Alternate procedure: Dissolve (S)-{7-cyano-4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl}-carbamic acid isopropyl ester (20 g; 34.64 mmoles) in tetrahydrofuran (170 mL) and ethanol (30 mL). Add hydrazine monohydrate (3.37 mL, 69.29 mmoles) using a syringe pump over 30 min. Stir the mixture at 22/24° C. for 3 h and then filter. Wash the cake with additional tetrahydrofuran (50 ml). Evaporate the combined mother liquors and purify the resulting residue by silica gel chromatography eluting with dichloromethane/(2M NH3 in methanol/) (98:2). Combine the fractions containing pure product and evaporate the solvent. Dry the solid to constant weight and then add over ethanol (50 mL). Heat the mixture to reflux until complete dissolution occurs and then allow to cool to room temperature overnight. Filter the solid and dry under vacuum to constant weight to provide 11.45 g (84%) of the title compound. MS (m/z): 390 (M+1). Chiral HPLC: ee>98% (Isomer 1, Chiralpak AD, EtOH/0.2% dimethylethylamine)

1. customover 30 min
2. filtrationfilter
3. washWash the cake with additional tetrahydrofuran (50 ml)
4. customEvaporate the combined mother liquors
5. custompurify the resulting residue by silica gel chromatography
6. washeluting with dichloromethane/(2M NH3 in methanol/) (98:2)
7. additionCombine the fractions containing pure product
8. customevaporate the solvent
9. customDry the solid to constant weight
10. additionadd over ethanol (50 mL)
11. temperatureHeat the mixture
12. temperatureto reflux until complete dissolution
13. temperatureto cool to room temperature overnight
14. filtrationFilter the solid
15. customdry under vacuum to constant weight