Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1) → 7-[(2,4-Dichlorophenyl)carbonyl]-3-(5-methyl-1,3-thiazol-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

4-[(2,4-Dichlorophenyl)carbonyl]-2-piperazinone (I6) (0.250 g, 0.915 mmol) was suspended in dry Dichloromethane (DCM) (3 mL) before treating with trimethyloxonium tetrafluoroborate (0.171 g, 1.098 mmol) and stirring for 16 hours at RT, under argon before adding 5-methyl-1,3-thiazole-4-carbohydrazide (I123)(0.216 g, 1.373 mmol) and stirring for a further 3 hours. DCM was removed by evaporation and the residue was dissolved in 1-butanol (3.00 mL) before heating at 110° C. for 19 hours. 3 Å molecular sieves were added and the reaction mixture was left heating for a further 6 hours before being cooled to RT over the weekend. The reaction was worked up by diluting with DCM (50 ml) and washing with saturated sodium bicarbonate solution (50 ml). The aqueous layer was extracted with DCM (2×30 ml), combined extracts were washed with brine (30 ml), dried (MgSO4), filtered and evaporated to afford a brown gum. The product was purified by MDAP (formic acid method), the desired fraction isolated and the solvent evaporated to afford a colourless gum. Placed in a registration vial and dried overnight to afford an off white foam of desired product in 122 mg.

1. stirringstirring for a further 3 hours
2. customDCM was removed by evaporation
3. dissolutionthe residue was dissolved in 1-butanol (3.00 mL)
4. temperaturebefore heating at 110° C. for 19 hours
5. addition3 Å molecular sieves were added
6. waitthe reaction mixture was left
7. temperatureheating for a further 6 hours
8. temperaturebefore being cooled to RT over the weekend
9. additionby diluting with DCM (50 ml)
10. washwashing with saturated sodium bicarbonate solution (50 ml)
11. extractionThe aqueous layer was extracted with DCM (2×30 ml)
12. washwere washed with brine (30 ml)
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. customevaporated
16. customto afford a brown gum
17. customThe product was purified by MDAP (formic acid method)
18. customthe desired fraction isolated
19. customthe solvent evaporated
20. customto afford a colourless gum
21. customdried overnight

ORD record

ord-c33502e4c4b844a1978979328e95e9cb

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2