1,4-Dioxane → HCID 86687691, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial charged with 2-methylphenylboronic acid (0.022 g, 0.158 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1′1′-biphenyl (4.33 mg, 10.54 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (7.99 mg, 10.54 μmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (From Example 160; 45 mg, 0.105 mmol), potassium phosphate (90 mg, 0.422 mmol), 1 mL dioxane and 0.25 mL water was heated to 150° C. in the microwave for 30 minutes. LC/MS showed mostly product, so the aqueous layer was removed. The reaction mixture was acidified with 4N HCl in dioxane then was concentrated. The crude product was purified by reverse phase column chromatography [PREP LC/MS-2 System Column: XBridge 19×100 mm 12230326114 03 Mobile phase: 0.1% NH4OH in water/acetonitrile Flow rate: 40 ml/min Inj: 2200 uL. Gradient: 10 min 10-40%_LV_NH3] yielding 1-(3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.017 g, 0.034 mmol, 32.6% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 2.36 (s, 3H) 3.68 (s, 3H) 6.95 (br. s., 1H) 7.08 (d, J=7.27 Hz, 1H) 7.14 (s, 1H) 7.27 (br. s., 1H) 7.29-7.44 (m, 5H) 7.78 (d, J=8.82 Hz, 1H) 7.97 (d, J=8.71 Hz, 1H) 8.08 (d, J=5.96 Hz, 1H) 8.18 (br. s., 1H) 8.52 (br. s., 1H) 8.62 (br. s., 1H) 8.68 (d, J=5.56 Hz, 1H); (M+H)+=483.0.

Provenance & Evidence