Water → (R)-N-(4-Cyano-2-methylphenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

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Reaction Steps

To a solution of 4-amino-3-methylbenzonitrile (30 mg, 226 μmol) in THF (2 mL) was added sodium hydride, 60% dispersion in mineral oil (15 μL, 339 pimp. The resulting mixture was then stirred at RT for 2 min. Then, (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg, 226 μmol, example 88) was added and the mixture was stirred at RT for overnight. Then, 26 mg of NaH (60% dispersion in mineral oil) was added and the mixture was stirred at RT for overnight. Then, H2O (0.2 mL) was added and the solvents were removed. The residue was then dissolved in a solution of DMSO and MeOH (1:1, 1.0 mL). The solution was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired product, which was dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP resin (polymerlabs, 200 mg/6 mL tube) and the resin was then washed with MeOH (2×0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound as a yellow solid. MS (ESI, positive ion) m/z: 436 (M+H).

Provenance & Evidence