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

Triethyloxonium tetrafluoroborate (314 mg, 1.654 mmol) was added under argon to a solution of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37)(481 mg, 1.654 mmol) in Dichloromethane (DCM) (4 ml). The reaction was stirred at room temperature for 40 min (until mixture became clear). 4-methyl-2-pyridinecarbohydrazide (I28)(300 mg, 1.985 mmol) was added and the mixture was stirred at room temperature overnight. The solvent was evaporated and 1-butanol (4.00 ml) was added. The reaction mixture was stirred at reflux 1 h 20 min—after 40 min, the reaction mixture became completely clear. The reaction mixture was diluted with ethyl acetate (I50 mL) and then extracted water (2×25 mL), with sat. NaHCO3 (25 mL) and with brine (25 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by MDAP. The resulting oil was triturated in hexane (10 mL) and ether (10 mL) and dried at 60° C. under vacuum for 5 days to afford the desired product in 189.9 mg as a white powder.

1. stirringthe mixture was stirred at room temperature overnight
2. customThe solvent was evaporated
3. addition1-butanol (4.00 ml) was added
4. stirringThe reaction mixture was stirred
5. temperatureat reflux 1 h 20 min—after 40 min
6. additionThe reaction mixture was diluted with ethyl acetate (I50 mL)
7. dry with materialThe organic layer was dried over MgSO4
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified by MDAP
10. customThe resulting oil was triturated in hexane (10 mL)
11. dry with materialether (10 mL) and dried at 60° C. under vacuum for 5 days

ORDレコード

ord-1c4fb83a071a4c98a2bac915fa72873a

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08501946B2