Hydrochloric Acid → 4'-({4-[4-Hydroxymethylbenzyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile

Temperatur

50 °C

A mixture of methyl 4-({6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}methyl)benzoate (2.8 g), 1N aqueous sodium hydroxide solution (30 mL), tetrahydrofuran (30 mL) and methanol (30 mL) was stirred at 50° C. for 3 hr. 1 N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (50 mL), N-methylmorpholine (0.67 mL) and ethyl chlorocarbonate (0.58 mL) was added at 0° C., and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was cooled to −15° C., sodium borohydride (0.57 g) and methanol (10 mL) were added, and the mixture was allowed to gradually warm to room temperature. The reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.86 g, 70%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe obtained ethyl acetate layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe obtained residue was dissolved in tetrahydrofuran (50 mL)
6. additionN-methylmorpholine (0.67 mL) and ethyl chlorocarbonate (0.58 mL) was added at 0° C.
7. stirringthe mixture was stirred at the same temperature for 2 hr
8. temperatureThe reaction mixture was cooled to −15° C.
9. additionsodium borohydride (0.57 g) and methanol (10 mL) were added
10. temperatureto gradually warm to room temperature
11. extractionThe reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate
12. washThe ethyl acetate layer was washed with saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe solvent was evaporated under reduced pressure
15. customThe obtained residue was purified by silica gel column chromatography

ORD-Eintrag

ord-fb48cbc0be314a4598e9d9842b8c2eab

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09115136B2