Dichloromethane → 5-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1,1-dimethylethyl 3-[[(5-chloro-2-thienyl)sulfonyl]({[2-(trimethylsilyl)ethyl]oxy}methyl)amino]-4-(methyloxy)-1H-indazole-1-carboxylate (for a preparation see Intermediate 7) (3.12 g, 5.43 mmol) in DMF (20 mL) was added a solution of sodium carbonate (0.864 g, 8.15 mmol) in water (20 mL) at room temperature. A white suspension was obtained and a warming of the medium was noticed. The resulting suspension was stirred overnight at 80° C., the reaction mixture was then cooled to room temperature, and more sodium carbonate (300 mg) was added. The resulting mixture was then stirred at 85° C. After 3 h of stirring, 50 mL of water and 50 mL of DCM were added to the reaction mixture. The organic layer was partitioned and the aqueous layer was further extracted with 30 mL of DCM. The organic solutions were combined, dried with an hydrophobic frit and concentrated under reduced pressure. The crude oil was purified by chromatography on two 100 g Si cartridges on Flashmaster, eluting with a 0 to 25% gradient of EtOAc in cyclohexane, over 25 min. The pure fractions were combined to give the title product as an orange gum (1.62 g, 63%) LCMS (System A) RT=1.41 min, ES+ve m/z 474/476 (M+H)+. Impure fractions were combined and repurified by chromatography on a 70 g silica cartridge on Flashmaster, eluting with a 0 to 25% gradient of EtOAc in cyclohexane over 40 min. Fractions containing pure product were combined to give more of the desired product (277 mg, 11%)

Provenance & Evidence