Hydrochloric Acid → 3-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}benzamide

To a solution of N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.485 mmol) in N,N-dimethylformamide (5 mL) was added chloroacetyl chloride (116 μL, 1.46 mmol), and the mixture was stirred at room temperature for 21 hr. 1N Hydrochloric acid (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL, 2×10 mL). The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL) and dried over anhydrous sodium sulfate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL). Triethylamine (202 μL, 1.46 mmol) and 1-methylpiperazine (162 μL, 1.46 mmol) were added thereto, and the mixture was stirred at 60° C. for 19 hr. A saturated aqueous sodium hydrogen carbonate solution (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL, 2×10 mL). The combined organic layer was washed with saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→94/6), and fractions containing the desired product were concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue. The obtained precipitate was collected by filtration and dried to give the title compound (147 mg, 55%) as a pale-yellow powder.

1. extractionthe mixture was extracted with ethyl acetate (30 mL, 2×10 mL)
2. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. customThe insoluble material was removed by filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
7. stirringthe mixture was stirred at 60° C. for 19 hr
8. extractionthe mixture was extracted with ethyl acetate (30 mL, 2×10 mL)
9. washThe combined organic layer was washed with saturated brine (10 mL)
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationThe insoluble material was filtered off
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→94/6), and fractions
14. additioncontaining the desired product
15. concentrationwere concentrated under reduced pressure
16. additionDiisopropyl ether was added to the obtained residue
17. filtrationThe obtained precipitate was collected by filtration
18. customdried

ORD-Eintrag

ord-cde8e14deba745bdab6e736a962beedb

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08304557B2