Cesium carbonate → (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

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Reaction Steps

Dissolve (S)-(7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (20 g, 70.59 mmoles; ee>98%, 2nd isomer on Chiracel OJ, 0.2% DMEA in Hexane/EtOH [80:20]) in dimethyl sulfoxide (160 mL) and add 2-(3-bromomethyl-pyridin-2-yl)-isoindole-1,3-dione (29.8 g, 84.71 mmol). Stir the mixture until a clear solution is obtained. Add cesium carbonate (46.4 g, 141.18 mmoles) and dimethylaminopyridine (875.5 mg, 7.06 mmol) in one portion. Stir the resulting mixture at 22/24° C. for 2 h. Add the mixture onto water (1.4 L). Stir the resulting suspension for 30 min and filter. Wash the resulting cake with water (100 ml). Dissolve the isolated wet solid in dichloromethane (750 mL) and separate the organic layer. Wash the organic layer with brine and evaporate the organic solvent. Purify the resulting material by silica gel chromatography, eluting with hexanes/acetone/CH2Cl2 (3/1/1) to obtain 24 g (58%). MS (m/z): 520 (M+1).

Provenance & Evidence