Citric Acid → 5-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide

Participants

Reaction Steps

A solution of 1,2,4-thiadiazol-5-amine (0.265 g, 2.62 mmol) and triethylamine (1.096 ml, 7.86 mmol) in 5 mL DCM was cooled to −78° C. and was treated with sulfuryl chloride (0.213 ml, 2.62 mmol). The cooling bath was removed, and the reaction mixture was allowed to stir for 20 minutes before 8-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (Intermediate R, 0.450 g, 1.311 mmol) was added as a solution in 5 mL DCM. The reaction mixture was allowed to stir for one hour before being poured into 1N citric acid and extracted with EtOAc. The organic layers were concentrated and purified by reverse phase column chromatography [RediSep Gold C-18 150 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide. [M+H]+=507.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.16 (s, 1H), 7.99 (s, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.55 (s, 1H), 7.48 (t, J=1.3 Hz, 1H), 7.03-7.15 (m, 3H), 6.92-6.97 (m, 1H), 4.25-4.45 (m, 2H), 3.75-3.86 (m, 1H), 3.28-3.35 (m, 1H), 2.46-2.63 (m, 2H)

Provenance & Evidence