Potassium Phosphate, Tribasic → N-(5-(6-methoxy-3-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide

HRID 539744Notes

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:14]=[CH:15][C:16]([CH3:26])=[C:17]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[CH:18]=1.[CH3:27]B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:12][O:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH3:27])=[C:3]([C:13]3[CH:14]=[CH:15][C:16]([CH3:26])=[C:17]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[CH:18]=3)[N:4]=2)[N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of N-(5-(3-bromo-6-methoxyimidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide (0.050 g, 0.119 mmol), methylboronic acid (0.357 mmol), tripotassium phosphate (0.714 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.0238 mmol) in toluene (4 mL) and water (0.4 mL) that has been degassed with N2 (5 minutes) is added Pd(OAc)2 (0.0119 mmol). The reaction mixture is heated at 100° C. for 14 hours, then cooled and concentrated to dryness. The crude product is purified via chromatography (hexanes to EtOAc) to afford 2.4 mg (6%) of the title compound as a white solid: Rf 0.64 (EtOAc); LCMS (m/z)=353.4 [M+H]+, tR=2.15 min. (compound same as Example 121)

Workup

customhas been degassed with N2 (5 minutes)
temperaturecooled
concentrationconcentrated to dryness
customThe crude product is purified via chromatography (hexanes to EtOAc)

Sources & evidence

ORD record: ord-34335bfcc8014e8e837bb9387c846a3d
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

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