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

Temperatur

110 °C

A solution of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37)(250 mg, 0.859 mmol) in dry dichloromethane (DCM) (2147 μl) was stirred at room temperature under an atmosphere of argon. Triethyloxonium tetrafluoroborate (179 mg, 0.945 mmol) was added to the stirred solution and the solution was stirred for 2 hours. 5-methyl-1,3-thiazole-4-carbohydrazide (I123) (162 mg, 1.031 mmol) was then added and the resulting solution was stirred for 65 hours (over the weekend), during which time the solvent evaporated. The residue was redissolved in 1-butanol (2147 p1) and the resulting mixture was heated to 110° C. for 3 hours. The solution was allowed to cool to room temperature before being concentrated under reduced pressure to give a yellow coloured oil. The oil was redissolved in DCM (approx. 30 ml) and the organics were subsequently washed with NaHCO3 (sat. aqueous solution approx. 20 ml) and brine (approx. 20 ml). The organics were dried over MgSO4, filtered and concentrated under reduced pressure to give a yellow coloured oil. The oil was chromatographed [SiO2, 0-10% MeOH in DCM] to give a pale yellow coloured oil. The oil was subsequently further purified using MDAP (formic acid method) to give a white coloured solid of desired material in 68 mg.

1. stirringthe resulting solution was stirred for 65 hours (over the weekend), during which time the solvent
2. customevaporated
3. dissolutionThe residue was redissolved in 1-butanol (2147 p1)
4. temperatureto cool to room temperature
5. concentrationbefore being concentrated under reduced pressure
6. customto give a yellow coloured oil
7. washthe organics were subsequently washed with NaHCO3 (sat. aqueous solution approx. 20 ml) and brine (approx. 20 ml)
8. dry with materialThe organics were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto give a yellow coloured oil
12. customThe oil was chromatographed [SiO2, 0-10% MeOH in DCM]
13. customto give a pale yellow coloured oil
14. customThe oil was subsequently further purified
15. customto give a white coloured solid of desired material in 68 mg

ORD-Eintrag

ord-d36201ea11584a9fa180313b3ca899b5

Quelldatensatz

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08501946B2