Pyrimidine-4-carbohydrazide → 7-[(2-Chlorophenyl)carbonyl]-3-(4-pyrimidinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

The title compound was prepared in a method analogous to the example E111. To a solution of 4-[(2-chlorophenyl)carbonyl]-2-piperazinone (I4) (269 mg, 1.127 mmol,) in Dichloromethane (5 ml) stirred under argon at room temp was added solid triethyloxonium tetrafluoroborate (214 mg, 1.127 mmol). The reaction mixture was stirred at RT for 1 hr. Solid 4-pyrimidinecarbohydrazide (I71 mg, 1.240 mmol, commerically available from e.g. Anichem, J&W PharmLab or Bepharm) 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 3 hr. The reaction mixture was cooled to room temperature and partitioned between Dichloromethane (˜50 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 (2×25 ml), dried over sodium sulphate and evaporated in vacuo to afford the crude product (−Z1) as a dark orange 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 washed with ether (˜10 ml) and dried overnight in a vacuum oven at 40° C. to afford the required product as a yellow solid in 74.1 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 3 hr
5. temperatureThe reaction mixture was cooled to room temperature
6. custompartitioned between Dichloromethane (˜50 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 (2×25 ml)
9. dry with materialdried over sodium sulphate
10. customevaporated in vacuo
11. customto afford the crude product (−Z1) as a dark orange oil

ORDレコード

ord-671a1daff42946918275a5b2d20d65f5

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08501946B2