1,4-Dioxane → HCID 86687524, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)phthalazine-6-sulfonamide (Intermediate AAAA) (56.22 mg, 0.118 mmol), (4-chloro-2-methoxyphenyl)boronic acid (Combi-Blocks, San Diego, Calif., 26.4 mg, 0.141 mmol), Pd(AmPhos)2Cl2 (4.17 mg, 5.89 μmol), potassium phosphate (75 mg, 0.354 mmol), 1,4-dioxane (442 μl), and water (147 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 fairly clean 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 filtered through diatomaceous earth with the aid of MeOH. The filtrate was concentrated, and the crude product was purified by chromatography on silica gel (12-g column, 0 to 6% MeOH/DCM) to give 1-(4-chloro-2-methoxyphenyl)-N-(thiazol-2-yl)phthalazine-6-sulfonamide (26.3 mg, 0.061 mmol, 51.5% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.97 (br. s., 1H), 9.92 (s, 1H), 8.73 (d, J=1.8 Hz, 1H), 8.22 (dd, J=1.9, 8.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.37 (d, J=1.9 Hz, 1H), 7.32-7.22 (m, 2H), 6.91 (d, J=4.6 Hz, 1H), 3.70 (s, 3H); m/z (ESI) 433.2 (M+H)+.

Provenance & Evidence