Sodium Hydroxide → HCID 66743161, compound

Participants

Reaction Conditions

Reaction Steps

In a 50 mL test tube, (S)-4-(5-(2-(tert-butyldimethylsilyloxy)-3-methoxypropoxy)pyridin-2-ylamino)-6-chloro-2-methylpyridazin-3(2H)-one (178 mg, 391 μmol) and 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (332 mg, 469 μmol) were combined in n-butanol (4 ml) to give a orange solution. 1 mL of water was added and the reaction mixture was purged with argon. X-PHOS (18.6 mg, 39.1 μmol) and potassium phosphate tribasic (166 mg, 782 μmol) were added. After argon was bubbled through the reaction mixture for 5 min. bis(dibenzylideneacetone)-palladium (0) (11.2 mg, 19.6 μmol) was added. The resulting suspension was heated in a oil bath at 110° C. for 1.5 hours. No (S)-4-(5-(2-(tert-butyldimethylsilyloxy)-3-methoxypropoxy)-pyridin-2-ylamino)-6-chloro-2-methylpyridazin-3(2H)-one remained by LCMS. Two main products were observed by LCMS, acetylated and deacetylated product. The reaction mixture was allowed to cool to 25° C. overnight. The reaction mixture was concentrated to small volume, poured into 75 mL H2O and extracted with EtOAc (3×75 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 20% to 60% EtOAc in hexanes) to afford 2 product peaks. These were combined and conc. to give 290 mg of a 1:1 mixture of acetylated and deacetylated product. This mixture was taken up in 15 mL THF and treated with 2 mL of 1N NaOH. The reaction mixture was heated to 60° C. and stirred for 20 h. Mostly complete by tlc. The reaction mixture was poured into 100 mL H2O and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 20% to 70% EtOAc in hexanes) to afford 217 mg of the desired product (75% yield). (M+H)+=745 m/e.

Provenance & Evidence