Triphenylphosphine → 6-[4-[4-[2-(4-Acetylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

温度

23.5 °C

Dichloromethane (225.0 mL) and 4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (50.0 g, 138 m mol) were charged to a suitable round bottom flask at 22-25° C. Triphenylphosphine (72.2 g, 275 m mol) and 1-[4-(2-hydroxy-ethyl)piperazin-1-yl]ethanone [CAS: 83502-55-0] (47.4 g, 275 m mol) were added successively to the reaction mass and stirred for 10 min at 22-25° C. Di-isopropyl azodicarboxylate (55.65 g, 275 m mol) in dichloromethane (75.0 mL) was added to the reaction mass slowly drop wise at 25-30° C. over a period of 60-90 min. The resulting reaction mass was stirred for 1.0 h at 25-30° C. to complete the reaction. n-Heptane (600.0 mL) was introduced to the reaction mass by drop wise addition over a period of 15-30 min at 22-25° C. and stirred for 30 min at the same temperature. Thus precipitated solid was filtered and washed with n-heptane (150.0 mL). The material was then suck dried for 30 min under reduced pressure. The crude material was purified by slurry washing in methanol (325.0 mL) at 22-25° C. The solid was then collected by filtration and washed with methanol (50.0 mL). The material was dried under reduced pressure with nitrogen gas bleed at 50° C. to afford the desired product 6-[4-[4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (61.2 g, 84%) as a free flowing solid.

1. waitslowly drop wise at 25-30° C. over a period of 60-90 min
2. customThe resulting reaction mass
3. stirringwas stirred for 1.0 h at 25-30° C.
4. customthe reaction
5. stirringstirred for 30 min at the same temperature
6. filtrationThus precipitated solid was filtered
7. washwashed with n-heptane (150.0 mL)
8. customThe material was then suck dried for 30 min under reduced pressure
9. customThe crude material was purified by slurry
10. washwashing in methanol (325.0 mL) at 22-25° C
11. filtrationThe solid was then collected by filtration
12. washwashed with methanol (50.0 mL)
13. customThe material was dried under reduced pressure with nitrogen gas
14. custombleed at 50° C.

ORDレコード

ord-19408ee4b1424e939dd674a0301a9928

出典データセット

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08258140B2