Hydrazine hydrate (1:1) → 2-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

Temperature

105 °C

A 500 mL round bottom flask was charged with 3-(6-chloropyridazin-3-yl)-2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (7.50 g, 22.5 mmol), 1-propanol (225 mL) and hydrazine hydrate (11.3 g, 225 mmol). The mixture was then heated at about 105° C. for about 10 h. The reaction mixture was cooled to ambient temperature and stirred overnight. The mixture was concentrated under reduced pressure to remove about ¾ of the volume. The remaining mixture was stirred with DCM (250 mL) and saturated aqueous NaHCO3 (200 mL). The layers were partitioned, the aqueous layer was diluted with water (100 mL) and extracted with DCM (2×200 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue was triturated with Et2O (50 mL) and the solid was collected by vacuum filtration. The filter cake was washed with additional Et2O (10 mL) and then dried in a vacuum oven for about 1 h at about 60° C. to give the title compound (4.59 g, 62%): LC/MS (Table 1, Method g) Rt=1.41 min; MS m/z: 329.1 (M+H)+.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationThe mixture was concentrated under reduced pressure
3. customto remove about ¾ of the volume
4. stirringThe remaining mixture was stirred with DCM (250 mL) and saturated aqueous NaHCO3 (200 mL)
5. customThe layers were partitioned
6. additionthe aqueous layer was diluted with water (100 mL)
7. extractionextracted with DCM (2×200 mL)
8. washThe combined organic extracts were washed with brine (100 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe resulting residue was triturated with Et2O (50 mL)
13. filtrationthe solid was collected by vacuum filtration
14. washThe filter cake was washed with additional Et2O (10 mL)
15. customdried in a vacuum oven for about 1 h at about 60° C.

ORD record

ord-73263a8e948c49baa107cbebbb5991c8

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188083B2