HCID 59455298, compound → HCID 178422186, compound

Participants

Reaction Steps

5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1-trityl-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (8.25 g, 12.2 mmol) in methanol (60 mL), dichloromethane (10 mL) and 1 N aqueous HCl solution (30 mL) was stirred at 50° C. for 1.5 hours. Most of the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and water (50 mL) was added. The pH of the mixture was adjusted to pH=7 with the addition of 1 N aqueous sodium hydroxide solution. The organic layer was separated and the aqueous layer further extracted with dichloromethane (2×100 mL). The organic extracts were combined, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane and hexane was then slowly added. The product recrystallized over 3 days. The crystalline product was filtered, washed with 50% dichloromethane/hexanes and dried under reduced pressure. The filtrate was collected, concentrated under reduced pressure and purified by column chromatography on silica gel Biotage 40S, eluting with 40-100% ethyl acetate/hexanes, to give additional product. The product from crystallization and the product from column chromatography were combined, dissolved in acetonitrile/water and lyophilized to afford 5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one as a white solid.

Provenance & Evidence