Potassium Phosphate, Tribasic → 4-(3'-fluoro-3-methoxy-[1,1'-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

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Reaction Steps

A vial was charged with 4-(4-chloro-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide (Example 524; 0.050 g, 0.115 mmol), (3-fluorophenyl)boronic acid (0.032 g, 0.230 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (2.365 mg, 5.76 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (4.36 mg, 5.76 μmol), and potassium phosphate (0.073 g, 0.346 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (0.524 ml) and Water (0.052 ml) were added in sequence. The vial was sealed and microwaved at 80° C. for three hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 4-(3′-fluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.47 (s, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.34 (s, 1H), 8.00-7.97 (m, 1H), 7.91-7.87 (m, 1H), 7.75-7.72 (m, 1H), 7.72-7.68 (m, 2H), 7.61-7.49 (m, 4H), 7.31-7.23 (m, 1H), 3.81 (s, 3H). m/z (ESI) 494.2 (M+H)+.

Provenance & Evidence