(1,1'-Binaphthalen)-2-yldi-tert-butylphosphine → 3-cyano-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 3-chloro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate RRR) (59.39 mg, 0.096 mmol), dicyanozinc (22.49 mg, 0.192 mmol), racemic-2-di-t-butylphosphino-1,1′-binaphthyl (Strem Chemical, Newburyport, Mass.) (7.63 mg, 0.019 mmol), palladium(ii) trifluoroacetate (3.18 mg, 9.58 μmol), and zinc (3.13 mg, 0.048 mmol). The vial was flushed with Ar (g), then DMAC (479 μl) was added. The vial was sealed and heated in a 95° C. heating bath for 15 h. The mixture was diluted with water and extracted with EtOAc (4× via pipette). The combined organic extracts were combined and concentrated. The residue was taken up in DCM (1 mL) and TFA (0.5 mL). After 30 min, the mixture was diluted with MeOH, then concentrated. The residue was purified by chromatography on silica gel (12-g column, 0 to 6% MeOH/DCM). The resulting material was concentrated from DCM (3×), then taken up in DCM and filtered through a membrane filter. The collected solid was washed with DCM (2×), dried under a flow of N2 (g), then dried under vacuum to give 3-cyano-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.99 (br. s., 1H), 8.95 (s, 1H), 8.70 (d, J=1.8 Hz, 1H), 8.07 (dd, J=1.9, 8.9 Hz, 1H), 7.83 (d, J=8.9 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.57-7.50 (m, 2H), 7.31 (d, J=4.5 Hz, 1H), 6.91 (d, J=4.6 Hz, 1H), 3.76 (s, 3H); m/z (ESI) 491.2 (M+H)+.

Provenance & Evidence