Water → (R)-N-(5-cyano-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-1-(4-(trifluoro-methyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

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Reaction Steps

To a solution of 5-amino-2-(2,2,2-trifluoroethoxy)nicotinonitrile (49 mg, 226 μmol) in THF (1.0 mL) was added sodium hydride, 60% dispersion in mineral oil (26 mg, 678 μmol). The resulting mixture was then stirred at RT for 15 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, a solution of H2O and MeOH (1:1, 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 mL). The solution mixture 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 washed with MeOH (2×0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound as a light yellow solid. MS (ESI, positive ion) m/z: 521 (M+H).

Provenance & Evidence