Hydrochloric Acid → HCID 178438665, compound

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%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additionthe residue was mixed with 3M hydrochloric acid (10 mL), acetone (20 mL) and tetrahydrofuran (10 mL)
6. stirringthe mixture was stirred at room temperature for 24 hr
7. customthe solvent was evaporated under reduced pressure
8. extractionthe residue was extracted with ethyl acetate
9. washThe organic layer was washed with saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. customThe residue obtained by purification by silica gel column chromatography
13. stirringthe mixture was stirred at 70° C. for 2 days
14. waitat room temperature for 3 days
15. customthe solvent was evaporated under reduced pressure
16. extractionthe residue was extracted with ethyl acetate
17. washThe organic layer was washed with saturated brine
18. dry with materialdried over anhydrous magnesium sulfate
19. customThe solvent was evaporated under reduced pressure
20. dissolutionthe residue was dissolved in tetrahydrofuran (2 mL)
21. additionSodium tetrahydroborate (0.034 g) was added at 0° C.
22. stirringthe reaction mixture was stirred at 0° C. for 2 hr
23. additionSaturated aqueous ammonium chloride solution was added to the reaction mixture
24. customthe solvent was evaporated under reduced pressure
25. extractionthe residue was extracted with ethyl acetate
26. washThe organic layer was washed with saturated brine
27. dry with materialdried over anhydrous magnesium sulfate
28. customThe solvent was evaporated under reduced pressure
29. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
30. additionTetrabutylammonium fluoride (1.0 mL, 1.0 M tetrahydrofuran solution) was added
31. stirringthe mixture was stirred at 70° C. for 2 hr
32. additionThe reaction mixture was added to 1 M hydrochloric acid
33. extractionthe mixture was extracted with ethyl acetate
34. washThe organic layer was washed with saturated brine
35. dry with materialdried over anhydrous magnesium sulfate
36. customThe solvent was evaporated under reduced pressure
37. customthe residue was purified by silica gel column chromatography

ORD record

ord-39dada3bc4064978bc566c17260b0a3a

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592431B2