Hydrochloric Acid → N-{6-[4-(4-benzyl-2-oxopiperazin-1-ylmethyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide dihydrochloride

To a solution of 4-benzylpiperazin-2-one (0.56 g, 2.95 mmol) in DMF (10 mL) was added 60% sodium hydride (0.12 g, 2.95 mmol), and this solution was stirred at room temperature for 30 minutes. 2-(4-chloromethylphenoxy)-5-nitropyridine (0.78 g, 2.95 mmol) was added to the reaction mixture, and the mixture was stirred for 1 hour at room temperature. To this mixture was added brine (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The remaining oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added iron powder (0.33 g, 5.89 mmol). This solution was stirred for 2 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution (50 mL) was added to the residue. The obtained mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The remaining oil was dissolved in THF (10 mL). To the resulting solution were added triethylamine (0.21 mL, 1.47 mmol) and 3,4-dichlorobenzoyl chloride (0.31 mL, 1.47 mmol), and this solution was stirred at room temperature for 2 hours. A saturated sodium bicarbonate solution (50 mL) was added to the solution, and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=40:1). The obtained oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate (1.5 mL, 6 mmol). The formed white powder was collected by suction filtration, to thereby yield 0.045 g of the title compound.

1. stirringthe mixture was stirred for 1 hour at room temperature
2. extractionextracted with ethyl acetate (50 mL)
3. washThe ethyl acetate layer was washed with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customevaporated under reduced pressure
6. dissolutionThe remaining oil was dissolved in ethyl acetate (5 mL)
7. stirringThis solution was stirred for 2 hours at room temperature
8. customThe resulting reaction solution
9. concentrationwas concentrated under reduced pressure
10. additiona saturated sodium bicarbonate solution (50 mL) was added to the residue
11. extractionThe obtained mixture was extracted with ethyl acetate (50 mL)
12. washThe ethyl acetate layer was washed with brine
13. dry with materialdried over anhydrous sodium sulfate
14. customevaporated
15. dissolutionThe remaining oil was dissolved in THF (10 mL)
16. stirringthis solution was stirred at room temperature for 2 hours
17. extractionextracted with ethyl acetate (50 mL)
18. washThe ethyl acetate layer was washed with brine
19. dry with materialdried over anhydrous magnesium sulfate
20. customevaporated under reduced pressure
21. customThe residue was purified by silica gel column chromatography (chloroform:methanol=40:1)
22. dissolutionThe obtained oil was dissolved in ethyl acetate (5 mL)
23. filtrationThe formed white powder was collected by suction filtration

ORD record

ord-61a981c313c349f2a4bde6249538d2be

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236826B2