Ammonia → 5-[6-(Hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 3.15 g of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compound B2b) and 218 ml of a saturated solution of ammonia in methanol was stirred in an autoclave at 120° C. for 3 h. The mixture was allowed to cool down to room temperature and concentrated to dryness to give the crude corresponding acid amide that was immediately used for the next step without further purification. The residue was dissolved in 180 ml tetrahydrofuran and to this solution is added 2.0 ml of tetra-n-butylammonium fluoride solution (˜75% in H2O) at 0° C. The reaction mixture was stirred at 0° C. for 12 h. The solvent was evaporated and the residue was treated with 250 ml dichloromethane and 60 ml saturated aqueous NaHCO3 solution. The resulting precipitate was dissolved by addition of propan-2-ol, the organic layer was separated, washed with 60 ml saturated aqueous NaHCO3 solution, dried with MgSO4 and concentrated under vacuum. The residue was suspended in 40 ml dichloromethane and stirred for one hour. The suspension was filtered, the filter cake washed with 20 ml dichloromethane and dried under vacuum to yield the title compound.

Provenance & Evidence