1,4-Dioxane → 5-(4-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 5-bromo-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (INTERMEDIATE D, 82.49 mg, 0.168 mmol), (4-cyano-2-methoxyphenyl)boronic acid (59.5 mg, 0.336 mmol), Pd(AmPhos)2Cl2 (5.96 mg, 8.41 μmol), potassium phosphate (107 mg, 0.505 mmol), 1,4-dioxane (631 μl), and water (210 μl). The vial was flushed with Ar (g), then sealed and heated in a Biotage Initiator microwave reactor for 30 min h at 90° C. 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 40 min, the mixture was diluted with MeOH and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane) to give a light-yellow solid. The material was concentrated from DCM, and then taken up in DCM. The solvent was mostly removed via pipette, then the solid was again concentrated from DCM to give 5-(4-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (35.5 mg, 0.084 mmol, 50.0% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.54 (d, J=1.9 Hz, 1H), 8.46 (s, 1H), 8.25 (d, J=8.3 Hz, 1H), 7.78-7.67 (m, 3H), 7.61-7.50 (m, 3H), 7.46 (d, J=7.6 Hz, 1H), 3.71 (s, 3H). m/z (ESI) 423.2 (M+H)+.

Provenance & Evidence