Citric Acid → HCID 71735778, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 1,2,4-thiadiazol-5-amine (2.67 g, 26.4 mmol) in 20 mL DCM was treated with triethylamine (3.68 ml, 26.4 mmol) and was allowed to stir for 10 minutes. The reaction mixture was then cooled to −78° C. and was treated with 1 equivalent of sulfuryl chloride. After stirring for 5 minutes, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional hour. LC/MS showed mostly product so the reaction mixture was filtered then concentrated. The resulting residue was dissolved in 10 mL THF and was added to a solution of 5-(2-bromo-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Intermediate D, 4.70 g, 13.20 mmol) and triethylamine (4.05 ml, 29.0 mmol) in 10 mL THF. After stirring for an additional 4 hours, the reaction mixture was poured into 1 N citric acid solution and was extracted with EtOAc. The organics were washed with brine, dried over MgSO4 and concentrated. The resulting residue was triturated with DCM providing a white solid. The washings were purified by silica gel column chromatography (0 to 100% EtOAc/heptane) and combined with the white solid yielding 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (6.90 g, 13.29 mmol). [M+H]+=518.9 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.04 (s, 1H), 7.97 (s, 1H), 7.81 (d, J=7.9 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.28 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.1 Hz, 1H), 7.01 (d, J=6.1 Hz, 1H), 4.34 (s, 2H), 3.30 (m, 2H), 2.47-2.58 (m, 2H)

Provenance & Evidence