Triethyloxonium tetrafluoroborate → 7-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-3-(1,3-thiazol-2-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Triethyloxonium tetrafluoroborate (144 mg, 0.756 mmol) was added to a suspension of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (200 mg, 0.687 mmol) in dry dichloromethane (DCM) (1.7 ml). The reaction was stirred at room temperature 1 h—everything dissolved. 1,3-thiazole-2-carbohydrazide (I50)(118 mg, 0.824 mmol) was added and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and 1-butanol (1.700 ml) was added to the residue. The resulting reaction mixture was stirred at reflux for 9 h. The reaction mixture was diluted with ethyl acetate (I25 mL) and washed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL). The resulting organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by MDAP (acidic method). The resulting residue was triturated with Et2O and dried 3 days at 50° C. under vacuum to afford desired product in 30.5 mg as a white solid.

1. dissolutiondissolved
2. stirringthe mixture was stirred at room temperature overnight
3. customThe solvent was evaporated under reduced pressure and 1-butanol (1.700 ml)
4. additionwas added to the residue
5. customThe resulting reaction mixture
6. stirringwas stirred
7. temperatureat reflux for 9 h
8. washwashed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL)
9. dry with materialThe resulting organic layer was dried over MgSO4
10. concentrationconcentrated under reduced pressure
11. customThe crude product was purified by MDAP (acidic method)
12. customThe resulting residue was triturated with Et2O
13. customdried 3 days at 50° C. under vacuum

ORD record

ord-d8f9301719f04aecb0111d8d18163097

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2