Hydrochloric Acid → HCID 68527183, compound

Temperature

60 °C

To a solution of 2-chloro-5-(4-trifluoromethylbenzoyl)pyridine (1.00 g, 3.5 mmol) in DMF (30 mL) were added N-(4-hydroxy-3-methylphenyl)glycine ethyl ester (0.81 g, 3.9 mmol), cesium carbonate (1.71 g, 5.2 mmol) and copper (I) iodide (200 mg, 1.05 mmol), and the resulting solution was stirred for 3.5 hours at 60° C. under an argon atmosphere. The resulting reaction solution was filtered and concentrated. To the residue was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 1.20 g of a yellow oil. The yellow oil was dissolved in THF (23 mL), and to the solution was added 1 M aqueous sodium hydroxide (3.9 mL, 3.9 mmol). The resulting solution was stirred for 3 hours at room temperature. This reaction solution was cooled with ice, and made to have a pH of 1 with 6 M hydrochloric acid. The resulting solution was extracted with ethyl acetate, and the ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, to thereby yield 1.04 g of a yellow oil. This yellow oil was dissolved in DMF (20 mL), and to the resulting solution were added 1-piperonylpiperazine (530 mg, 2.4 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (560 mg, 2.9 mmol) and 1-hydroxybenzotriazole monohydrate (390 mg, 2.6 mmol), and the resulting solution was stirred for 15 hours at room temperature. The reaction solution was concentrated under reduced pressure, and to the residue was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2→ethyl acetate), to thereby yield 280 mg of a yellow oil. To this oil was added diethyl ether and left to stand. Precipitated matter, was collected by filtration, to thereby yield 220 mg of the title compound.

1. customThe resulting reaction solution
2. filtrationwas filtered
3. concentrationconcentrated
4. additionTo the residue was added water
5. extractionextracted with ethyl acetate
6. washThe ethyl acetate layer was washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe solvent was evaporated
9. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1)
10. dissolutionThe yellow oil was dissolved in THF (23 mL)
11. stirringThe resulting solution was stirred for 3 hours at room temperature
12. temperatureThis reaction solution was cooled with ice
13. extractionThe resulting solution was extracted with ethyl acetate
14. washthe ethyl acetate layer was washed with water
15. dry with materialdried over anhydrous magnesium sulfate
16. customThe solvent was evaporated under reduced pressure
17. dissolutionThis yellow oil was dissolved in DMF (20 mL)
18. stirringthe resulting solution was stirred for 15 hours at room temperature
19. concentrationThe reaction solution was concentrated under reduced pressure
20. additionto the residue was added water
21. extractionextracted with ethyl acetate
22. washThe ethyl acetate layer was washed with water
23. dry with materialdried over anhydrous magnesium sulfate
24. customevaporated
25. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2→ethyl acetate)
26. additionTo this oil was added diethyl ether
27. waitleft
28. customPrecipitated matter
29. filtrationwas collected by filtration

ORD record

ord-f64250e8747d4e38ab8fd8f95b4bdf3c

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236826B2