Hydrochloric Acid → HCID 178438665, compound

Participants

Reaction Steps

A mixture of 4′-[(4-{trans-4-[4-(1,3-dioxan-2-yl)-2-hydroxybutoxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.71 g), tert-butylchlorodiphenylsilane (0.47 g), imidazole (0.11 g), N,N-dimethylaminopyridine (0.015 g) and tetrahydrofuran (8 mL) was stirred at room temperature for 7 days. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was mixed with 3M hydrochloric acid (10 mL), acetone (20 mL) and tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 24 hr. The reaction mixture was neutralized, the solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by purification by silica gel column chromatography was mixed with 3M hydrochloric acid (10 mL) and tetrahydrofuran (20 mL), and the mixture was stirred at 70° C. for 2 days and then at room temperature for 3 days. The reaction mixture was neutralized, the solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (2 mL) and methanol (4 mL). Sodium tetrahydroborate (0.034 g) was added at 0° C., and the reaction mixture was stirred at 0° C. for 2 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, the solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL). Tetrabutylammonium fluoride (1.0 mL, 1.0 M tetrahydrofuran solution) was added, and the mixture was stirred at 70° C. for 2 hr. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.17 g, 26%).

Provenance & Evidence