Methanol → Ethyl 6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate

Temperatur

70 °C

A 250 mL pear flask was charged with 2-(2,4-difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (7.90 g, 24.1 mmol) and MeOH (70 mL). To the flask was added ethyl 2-oxoacetate (Fluka, 5.72 mL, 28.9 mmol) and the mixture was heated to about 70° C. for about 1 h, at which point the starting material was consumed. The suspension was cooled to ambient temperature and the MeOH was removed under reduced pressure to give a brown solid. To the flask was added DCM (70 mL) and iodobenzene diacetate (10.1 g, 31.3 mmol) resulting in the formation of a dark solution. After about 1 h, the solution was poured into additional DCM (100 mL) and washed with water and brine. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated to give a dark brown solid. The solid was triturated with Et2O (about 30 mL) and a brown solid was collected by vacuum filtration. A second trituration was carried out with Et2O/MeOH (9:1, 45 mL) to give the title compound as a light brown solid (7.25 g, 73%): LC/MS (Table 1, Method h) Rt=1.27 min; MS m/z: 411.1 (M+H)+.

1. customwas consumed
2. temperatureThe suspension was cooled to ambient temperature
3. customthe MeOH was removed under reduced pressure
4. customto give a brown solid
5. customresulting in the formation of a dark solution
6. washwashed with water and brine
7. customThe layers were separated
8. dry with materialthe organic solution was dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a dark brown solid
12. customThe solid was triturated with Et2O (about 30 mL)
13. filtrationa brown solid was collected by vacuum filtration

ORD-Eintrag

ord-62a4fb81261d45b998fee73abefe41f6

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08188083B2