4-Fluorophenyl isocyanate → 8-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

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Reaction Steps

A solution of 8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.4 g, 1.4 mmol) and diisopropylethylamine (0.5 mL, 2.9 mmol) in anhydrous 1,2-dichloroethane (10 mL) was treated with 4-fluorophenyl isocyanate (0.14 mL, 1.2 mmol) and stirred at RT for 16 h. The solvent was removed under vacuum and the residue was purified by preparative HPLC [gradient 10-90% MeCN (0.1% TFA)/H2O (0.1% TFA)] to give the pure product which was dissolved in methanol (10 mL) and neutralized by passing the solution through a Polymer Lab-HCO3 Macroporous resin cartridge, and the filtrate was concentrated to give 8-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide as a white solid. MS (ESI pos. ion) m/z: 433 (M+1).

Provenance & Evidence