Ammonia → HCID 57647133, compound

Temperature

140 °C

A mixture of 3-(methylsulfinyl)-6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine (550 mg, 1.42 mmol) in Ac2O (5 mL) and NaOAc (582 mg, 4.3 mmol) was heated at 140° C. for 2 h. The volatiles were evaporated and the residue was dissolved and re-evaporated with (3×5 mL) of benzene. The product was dried under high vacuum and dissolved in CH2Cl2/MeOH (2:1, 7 mL) followed by addition of magnesium monoperoxyphthalate (1.0 g, 1.72 mmol). The reaction mixture was stirred for 16 h after which it was filtered and the filtrate washed with saturated aqueous NaHCO3 (50 mL), dried over Na2SO4 and evaporated. The residue was dissolved in THF/MeOH (2:1, 7 mL) and treated with aqueous NaOH (1.4 mL, 1.42 mmol, 1N) and stirred for 1 h. The solvent was evaporated and the residue dissolved and re-evaporated with (2×5 mL) of EtOH and then benzene (5 mL). The mixture was dried under high vacuum, triturated with Et2O (2×5 mL). CH2Cl2 (5 mL) was added and the mixture was cooled to 0° C. SO2Cl2 (0.11 mL, 1.42 mmol) was added and the mixture was stirred at room temperature for 1 h. The mixture was then cooled to 0° C., treated with aqueous NH3 (5 mL) and warmed to room temperature. After 1 h, the mixture was diluted with water (5 mL), extracted with (3×20 mL) of EtOAc and dried over Na2SO4. Evaporation of the solvent followed by purification by Combiflash chromatography (SiO2, gradient elution 40-60% EtOAc/hexanes) afforded the desired product. 1H NMR (500 MHz, acetone-d6): δ 1.94-1.98 (m, 2H), 2.14-2.20 (m, 2H), 3.95-4.09 (m, 4H), 5.03-5.05 (m, 1H), 6.69 (s, 2H), 7.12 (t, 1H), 7.39 (d, 2H), 7.62-7.68 (m, 2H), 7.79 (d, 1H). MS (+ESI) m/z 403 (MH+).

1. customThe volatiles were evaporated
2. dissolutionthe residue was dissolved
3. customre-evaporated with (3×5 mL) of benzene
4. customThe product was dried under high vacuum
5. dissolutiondissolved in CH2Cl2/MeOH (2:1, 7 mL)
6. filtrationwas filtered
7. washthe filtrate washed with saturated aqueous NaHCO3 (50 mL)
8. dry with materialdried over Na2SO4
9. customevaporated
10. dissolutionThe residue was dissolved in THF/MeOH (2:1, 7 mL)
11. stirringstirred for 1 h
12. customThe solvent was evaporated
13. dissolutionthe residue dissolved
14. customre-evaporated with (2×5 mL) of EtOH
15. customThe mixture was dried under high vacuum
16. customtriturated with Et2O (2×5 mL)
17. additionCH2Cl2 (5 mL) was added
18. temperaturethe mixture was cooled to 0° C
19. stirringthe mixture was stirred at room temperature for 1 h
20. temperatureThe mixture was then cooled to 0° C.
21. temperaturewarmed to room temperature
22. waitAfter 1 h
23. extractionextracted with (3×20 mL) of EtOAc
24. dry with materialdried over Na2SO4
25. customEvaporation of the solvent
26. customfollowed by purification by Combiflash chromatography (SiO2, gradient elution 40-60% EtOAc/hexanes)

ORD record

ord-207fd24bdecd4e05946b750ba85e8d3e

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07799787B2