Isopropanol → HCID 67983586, compound

HRID 539774Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:25])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH3:24])=[C:15]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=3)[N:10]=2)[N:7]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+].CC(O)C>O>[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:25])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH3:24])=[C:15]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=3)[N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of N-(5-(6-chloro-3-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide (0.100 g, 0.280 mmol), 4-fluorophenylboronic acid (0.420 mmol), Na2CO3 (0.840 mmol), 2-propanol (9 mL) and water (3 mL) that has been degassed with N2 (5 minutes) is added PdCl2(PPh3)2(0.0280). The mixture is heated at 80° C. for 12 hours, 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 using a gradient of hexanes to EtOAc to afford the title compound (0.073 g, 62%) as a yellow solid: Rf 0.29 (1:1 EtOAc:hexanes); LCMS (m/z)=417.5 [M+H]+, tR=2.71 min. (compound same as Example 312)

Workup

customhas been degassed with N2 (5 minutes)
additionis added PdCl2(PPh3)2(0.0280)
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

Sources & evidence

ORD record: ord-0bad363833334c1b820344959c32d920
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

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