2-(3-Bromo-4-(trifluoromethyl)phenyl)-6-ethoxyimidazo[1,2-b]pyridazine → 6-Ethoxy-2-(3-(pyridin-2-yl)-4-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazine

HRID 539769Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH3:22])=[N:16][N:15]3[CH:23]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[Br-].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Zn+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:21]([O:20][C:17]1[CH:18]=[CH:19][C:14]2[N:15]([CH:23]=[C:12]([C:4]3[CH:5]=[CH:6][C:7]([C:8]([F:11])([F:10])[F:9])=[C:2]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=4)[CH:3]=3)[N:13]=2)[N:16]=1)[CH3:22]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-(3-bromo-4-(trifluoromethyl)phenyl)-6-ethoxyimidazo[1,2-b]pyridazine (0.025 g, 0.0647 mmol) in THF (0.647 mL) containing pyridin-2-ylzinc(II) bromide (0.323 mmol) is added Pd(dppf)Cl2 (0.0194 mmol). The mixture is heated at 60° C. for 12 hours, then cooled, quenched with sat. aqueous NaHCO3 (1 mL) and extracted with CH2Cl2 (3×3 mL). Organic layer is collected and concentrated to dryness. The crude product is purified via preparative TLC using CH2Cl2:EtOAc:methanol (1:1:0.1) to afford 0.0022 g (9%) of the title compound as a white solid: Rf 0.35 (1:1 EtOAc:hexanes); LCMS (m/z)=385.4 [M+H]+, tR=2.69 min. (compound same as Example 218)

Workup

temperaturecooled
customquenched with sat. aqueous NaHCO3 (1 mL)
extractionextracted with CH2Cl2 (3×3 mL)
customOrganic layer is collected
concentrationconcentrated to dryness
customThe crude product is purified via preparative TLC

Sources & evidence

ORD record: ord-f15977e6948c4d77a3469e8c6f10776d
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

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