Hydrochloric Acid → 6-(Piperidin-1-yl)-3-(piperidin-3-yl)[1,2,4]triazolo[4,3-b]pyridazine

A mixture of 1-[(benzyloxy)carbonyl]piperidine-3-carboxylic acid (2.44 g), 3-chloro-6-hydrazinopyridazine (1.34 g), WSCD hydrochloride (2.13 g) and methylene chloride (60 ml) was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure and extracted with ethyl acetate. The extract was washed successively with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant reside was combined with acetic acid (80 ml), stirred at 100° C. for 2 days, and then the solvent was distilled off under reduced pressure. The resultant crude crystals were washed with ethanol, and stirred with heating under reflux in piperidine (10 ml) for 3 hours. The reaction solution was concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: chloroform:methanol=97:3). The resultant colorless solids were combined with ethanol (40 ml) and 10% palladium-carbon (150 mg), and stirred under hydrogen atmosphere at room temperature for 6 hours, and then the catalyst was filtered off. The resultant filtrate was concentrated under reduced pressure to obtain 6-piperidin-1-yl-3-piperidin-3-yl-1,2,4-triazolo[4,3-b]pyridazine (1.18 g) as a colorless amorphous.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. extractionextracted with ethyl acetate
3. washThe extract was washed successively with water and brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. stirringstirred at 100° C. for 2 days
7. distillationthe solvent was distilled off under reduced pressure
8. washThe resultant crude crystals were washed with ethanol
9. stirringstirred
10. temperaturewith heating
11. temperatureunder reflux in piperidine (10 ml) for 3 hours
12. concentrationThe reaction solution was concentrated under reduced pressure
13. custompurified by silica gel column chromatography (eluent: chloroform:methanol=97:3)
14. stirringstirred under hydrogen atmosphere at room temperature for 6 hours
15. filtrationthe catalyst was filtered off
16. concentrationThe resultant filtrate was concentrated under reduced pressure

ORD-Eintrag

ord-170012020a25498db2ce5a9ec298f6db

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07173033B2