Triethyloxonium tetrafluoroborate → 7-[(2-Chlorophenyl)carbonyl]-3-(5-fluoro-2-pyridinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

The title compound was prepared in an analogous method to that described in E111. To a solution of 4-[(2-chlorophenyl)carbonyl]-2-piperazinone (I4) (225 mg, 0.943 mmol) in Dichloromethane (5 ml) stirred under argon at room temp was added solid triethyloxonium tetrafluoroborate (179 mg, 0.943 mmol). The reaction mixture was stirred at RT for 2 hr. Solid 5-fluoro-2-pyridinecarbohydrazide (I24) (161 mg, 1.037 mmol) was added and the reaction mixture stirred at RT for 18 hr. The solvent was evaporated in vacuo, and the residue dissolved in n-butanol (5 ml) and stirred at 120° C. for 4 hr. The reaction mixture was cooled to room temperature and partitioned between Dichloromethane (˜25 ml) and saturated brine (˜25 ml). The aqueous phase was extracted with Dichloromethane (2×25 ml) and the combined organic extracts washed with saturated brine (˜25 ml), dried over sodium sulphate, and evaporated in vacuo to afford the crude product as a yellow oil. This was dissolved in 1:1 MeOH:DMSO and purified by Open Access Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier. The solvent was evaporated in vacuo and the residue dried overnight in a vacuum oven at 40° C. to give the required product as a white powder in 126.4 mg.

1. stirringthe reaction mixture stirred at RT for 18 hr
2. customThe solvent was evaporated in vacuo
3. dissolutionthe residue dissolved in n-butanol (5 ml)
4. stirringstirred at 120° C. for 4 hr
5. temperatureThe reaction mixture was cooled to room temperature
6. custompartitioned between Dichloromethane (˜25 ml) and saturated brine (˜25 ml)
7. extractionThe aqueous phase was extracted with Dichloromethane (2×25 ml)
8. washthe combined organic extracts washed with saturated brine (˜25 ml)
9. dry with materialdried over sodium sulphate
10. customevaporated in vacuo
11. customto afford the crude product as a yellow oil

ORD record

ord-9571d50db0c0492e997543379639d5ef

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2