Sodium Carbonate → 3-(4-Fluorophenyl)-6-methoxy-2-(4-methyl-3-nitrophenyl)imidazo[1,2-b]pyridazine

HRID 539739Notes

Reaction equation

Br[C:2]1[N:6]2[N:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>CC(O)C.O>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[N:6]3[N:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]3=[N:4][C:3]=2[C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=2)=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred mixture of 3-bromo-6-methoxy-2-(4-methyl-3-nitrophenyl)imidazo[1,2-b]pyridazine (0.100 g, 0.275 mmol), 4-fluorophenylboronic acid (0.412 mmol), Na2CO3 (0.825 mmol) in 2-propanol (6 mL) and water (2 mL) that has been degassed with N2 (5 minutes) is added PdCl2(PPh3)2(0.0275 g). The reaction mixture is heated at 80° C. for 6 hours, cooled, diluted with sat. aqueous NaHCO3 (50 mL) and extracted with EtOAc (3×25 mL). Organic layer is collected, dried over Na2SO4, filtered and concentrated to dryness. The crude product is purified via chromatography (hexanes to EtOAc) to afford 0.092 g (88%) of the title compound as a yellow solid: Rf 0.47 (1:1 EtOAc:hexanes); LCMS (m/z)=379.4 [M+H]+, tR=3.07 min.

Workup

customhas been degassed with N2 (5 minutes)
additionis added PdCl2(PPh3)2(0.0275 g)
temperaturecooled
additiondiluted with sat. aqueous NaHCO3 (50 mL)
extractionextracted with EtOAc (3×25 mL)
customOrganic layer is collected
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated to dryness
customThe crude product is purified via chromatography (hexanes to EtOAc)

Sources & evidence

ORD record: ord-a814a4c794af4f94b87cb54f68dee6e5
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

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