Hydrochloric Acid → HCID 71737517, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial charged with Pd(Amphos)2Cl2 (9.43 mg, 0.013 mmol), (4-chloro-2-methoxy)phenylboronic acid (0.050 g, 0.266 mmol), 5-bromo-N-(1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.100 g, 0.266 mmol), potassium phosphate (0.339 g, 1.599 mmol), 1.5 mL of dioxane and 0.25 mL of water was heated to 150° C. in the microwave for 30 minutes. (3,4-difluorophenyl)boronic acid (0.053 g, 0.333 mmol) and an additional portion of Pd(Amphos)2Cl2 (9.43 mg, 0.013 mmol) were added, and the reaction mixture was heated to 150° C. in the microwave for an additional 30 minutes. The aqueous layer was removed, and the reaction mixture was treated with HCl (4N in dioxane) (0.266 ml, 1.066 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(3′,4′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.048 g, 0.093 mmol, 35.0% yield). 1H NMR (MeCN-d3) δ: 8.31 (s, 1H), 7.65 (ddd, J=12.2, 7.8, 2.2 Hz, 1H), 7.52 (dddt, J=7.1, 4.3, 2.7, 1.2 Hz, 1H), 7.37 (dt, J=10.6, 8.5 Hz, 1H), 7.14-7.27 (m, 4H), 7.07-7.12 (m, 1H), 6.99-7.05 (m, 1H), 4.20-4.41 (m, 2H), 3.81 (s, 3H), 3.30-3.39 (m, 1H), 3.12-3.24 (m, 1H), 2.63-2.76 (m, 1H), 2.42-2.55 (m, 1H); (M+H)+=515.0.

Provenance & Evidence