Hydrazine hydrate (1:1) → (S)-[4-(2-Amino-pyridin-3-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

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Reaction Conditions

Reaction Steps

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)

Provenance & Evidence