Hydrochloric Acid → HCID 86687698, compound

Participants

Reaction Steps

A solution of 2-dicyclohexylphosphino-2′,6′-dimethoxy-1′1′-biphenyl (4.59 mg, 0.011 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) methyl-t-butylether (8.48 mg, 0.011 mmol), potassium phosphate (0.190 g, 0.895 mmol), cyclopropylboronic acid (0.038 g, 0.448 mmol), and 1-(5-chloro-4-(difluoromethyl)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (From Example 457; 0.108 g, 0.224 mmol) in 1.5 mL dioxane/0.5 mL water was heated to 180° C. in the microwave for 45 minutes. LC/MS showed product, so the aqueous layer was removed. The reaction mixture was treated with HCl (4N in dioxane) (0.224 ml, 0.895 mmol) and was allowed to stir for 10 minutes. The reaction mixture was then concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(5-cyclopropyl-4-(difluoromethyl)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.040 g, 0.083 mmol, 37.0% yield). 1H NMR (MeCN-d3) δ: 8.65 (d, J=5.7 Hz, 1H), 8.58 (s, 1H), 8.44 (s, 1H), 8.14 (d, J=6.3 Hz, 1H), 7.86-7.95 (m, 2H), 7.63-7.69 (m, 1H), 7.15-7.45 (m, 2H), 7.12 (s, 1H), 6.96 (s, J=6.3, 1H), 3.67 (s, 3H), 2.03-2.14 (m, 1H), 0.88-1.00 (m, 2H), 0.59-0.70 (m, 2H); (M+H)+=483.0.

Provenance & Evidence