1,4-Dioxane → HCID 86687526, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-chloro-N-(5-fluorothiazol-2-yl)-N-(4-methoxybenzyl)phthalazine-6-sulfonamide (Intermediate CCCC) (55.94 mg, 0.120 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (Combi-Blocks, San Diego, Calif., 31.8 mg, 0.144 mmol), Pd(AmPhos)2Cl2 (4.26 mg, 6.02 μmol), potassium phosphate (77 mg, 0.361 mmol), 1,4-dioxane (451 μl), and water (150 μl). The vial was flushed with Ar (g), then sealed and heated in a microwave reactor for 30 min 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 30 min, the mixture was diluted with MeOH and concentrated, and the crude product was purified by chromatography on silica gel (12-g column, 0 to 7% MeOH/DCM) to give N-(5-fluorothiazol-2-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonamide (35.18 mg, 0.073 mmol, 60.4% yield) as a cream-colored solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.88 (s, 1H), 9.96 (s, 1H), 8.76 (d, J=1.9 Hz, 1H), 8.22 (dd, J=1.9, 8.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.60-7.52 (m, 2H), 7.41 (s, 1H), 3.77 (s, 3H); m/z (ESI) 485.2 (M+H)+.

Provenance & Evidence