1,4-Dioxane → HCID 86687488, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate PPP) (58.34 mg, 0.118 mmol), (2-methoxyphenyl)boronic acid (35.9 mg, 0.236 mmol), Pd(AmPhos)2Cl2 (8.36 mg, 0.012 mmol), potassium phosphate (75 mg, 0.354 mmol), 1,4-dioxane (443 μl), and water (148 μl). The vial was flushed with Ar (g), then sealed and heated in a microwave reactor for 30 min h at 90° C. LC/MS showed conversion to the protected product. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 2 h, the mixture was diluted with MeOH and concentrated, and the crude product was purified by chromatography on silica gel (12-g column, 3% MeOH/DCM) to give 4-fluoro-1-(2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (49 mg, 0.118 mmol, 100% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.99 (br. s., 1H), 8.70 (d, J=1.7 Hz, 1H), 8.49 (d, J=1.8 Hz, 1H), 7.99 (dd, J=1.8, 8.9 Hz, 1H), 7.78 (dd, J=1.8, 8.8 Hz, 1H), 7.58-7.50 (m, 1H), 7.38-7.27 (m, 2H), 7.23 (d, J=8.3 Hz, 1H), 7.16-7.10 (m, 1H), 6.89 (d, J=4.6 Hz, 1H), 3.65 (s, 3H); m/z (ESI) 416.2 (M+H)+.

Provenance & Evidence