Potassium Carbonate → 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A microwave vial was charged with 1-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate EEEEE; 0.052 g, 0.095 mmol), (3,4-difluorophenyl)boronic acid (0.022 g, 0.142 mmol), potassium carbonate (0.039 g, 0.285 mmol), and Pd(Ph3P)4 (10.96 mg, 9.49 μmol). The vial was flushed with Ar (g), then Dioxane (0.712 mL) and Water (0.237 mL) were added. The reaction was microwaved at 90° C. for one hour. 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 0-50% EtOAc:Heptane) to afford 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred overnight at room temperature. Triflic acid (0.050 mL, 0.563 mmol) was added and the reaction was stirred for one hour. The reaction was concentrated and the material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.78-8.71 (m, 2H), 8.59 (s, 1H), 8.33-8.28 (m, 1H), 8.28-8.23 (m, 2H), 8.13 (br. s., 1H), 8.02 (d, J=1.9 Hz, 1H), 7.98 (d, J=7.6 Hz, 2H), 7.88 (d, J=7.9 Hz, 2H), 7.62 (td, J=8.6, 10.4 Hz, 1H), 7.03 (d, J=6.0 Hz, 1H), 3.91 (s, 3H). m/z (ESI) 506.1 (M+H)+.

Provenance & Evidence