Acetic Acid → 6-chloro-2-methyl-4-(1'-oxetan-3-yl-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino)-2H-pyridazin-3-one

Temperature

55 °C

To a solution of 6-chloro-2-methyl-4-(5-(piperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (639 mg, 2.00 mmol, Eq: 1.00) and oxetan-3-one (288 mg, 4.00 mmol, Eq: 2.0) in THF (10 ml) was added acetic acid (360 mg, 343 μl, 5.99 mmol, Eq: 3.0). The reaction mixture stirred under N2, at 55° C. for 1 h. Then sodium triacetoxyborohydride (847 mg, 4.00 mmol, Eq: 2.0) was added and the mixture was stirred at 65° C. for 2 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was partitioned between DCM and saturated NaHCO3. The layers were separated and the organic layer was washed with water. The organic layer was then dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 40% (60:10:1 DCM:MeOH:NH4OH)/DCM) gradient) to give 6-chloro-2-methyl-4-(1′-oxetan-3-yl-1′,2′,3′,4′,5′,6′-hexahydro-[3,4]bipyridinyl-6-ylamino)-2H-pyridazin-3-one (453 mg, 60%). LC/MS-ESI observed [M+H]+ 376. 1H NMR in CDCl3 is consistent with desired product.

1. stirringthe mixture was stirred at 65° C. for 2 h
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated in vacuo
4. customThe residue was partitioned between DCM and saturated NaHCO3
5. customThe layers were separated
6. washthe organic layer was washed with water
7. dry with materialThe organic layer was then dried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 40% (60:10:1 DCM:MeOH:NH4OH)/DCM) gradient)

ORD record

ord-964531da739d45f29622543bdb1d3d60

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481540B2