Citric Acid → HCID 71736901, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-fluorothiazol-2-amine hydrochloride (Milestone Pharmatech, Brunswick, N.J., 0.692 g, 4.48 mmol) and imidazole (1.219 g, 17.91 mmol) in 10 mL DCM was cooled to −78° C. and was treated with sulfuryl chloride (0.364 ml, 4.48 mmol). After stirring for 10 minutes, the reaction mixture was placed in a 0° C. bath and was allowed to stir for one hour at which point about 3 mL heptane was added, and the organics were decanted off. The resulting solid was treated with a solution of 5-(2-(4-methyl-1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.800 g, 2.239 mmol) in 15 mL DCM followed by DIPEA (4.69 ml, 26.9 mmol) and was heated to 80° C. for 30 minutes. The reaction mixture was poured into 1N citric acid solution and was extracted with EtOAc. The organics were concentrated then purified directly by reverse phase column chromatography [RediSep Gold C18 150 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding N-(5-fluorothiazol-2-yl)-5-(2-(4-methyl-1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.005 g, 9.30 μmol). [M+H]+=538.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 7.93 (s, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.28 (s, 1H), 7.23 (s, 1H), 7.09-7.20 (m, 2H), 7.02 (d, J=7.0 Hz, 1H), 6.99 (d, J=0.7 Hz, 1H), 4.25-4.43 (m, 2H), 3.78-3.83 (m, 1H), 3.18-3.28 (m, 1H), 2.45-2.55 (m, 1H), 2.33-2.42 (m, 1H), 2.14 (s, 3H)

Provenance & Evidence