Sodium Hydroxide → 2-(3,4-difluorophenyl)-4-(2-hydroxy-2-methyl-1-propoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)-pyridazinone

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3,4-difluorophenyl)-4-(2-hydroxy-2-methyl- -propoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (139 mg, 0.309 mmol) and di-t-butylazodicarboxylate (71.2 mg, 0.309 mmol) in THF (25 mL) at −78° C. was added dropwise a 1M solution of NaHMDS (0.93 mL, 0.928 mmol) in THF. After addition the reaction was stirred another 45 min at −78° C. (or until TLC indicated a disappearance of starting material) and then was treated with 1N NaOH (20 mL). The reaction mixture was stirred at room temperature for the next 18 h. Sodium acetate trihydrate (758 mg, 5.57 mmol) was added followed by addition of hydroxylamine-O-sulphonic acid (630 mg, 5.57 mmol) and H2O (50 mL). The resulting mixture was stirred at ambient temperature for the next 18 hours and then extracted with EtOAc. The extract was washed with water, brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 1:1 hexanes-EtOAc) to provide the title compound (yield: 25 mg; 18%). mp 65–69° C; 1H NMR (300 MHz, DMSO-d6) δ 1.0 (s, 6H), 4.2 (s, 2H), 4.56 (s, 1H), 7.51 (m, 3H), 7.6 (m, 1H), 7.85 (m, 1H), 7.95 (s, 4H), 8.21 (s, 1H); MS (DCI/NH3) m/z 451 (M+H)+, 467 (M+NH4)+.

Provenance & Evidence