Potassium Acetate → 2-(4-Methyl-3-nitro-phenyl)-6-[2-(trifluoromethyl)-3-pyridyl]imidazo[2,1-f]pyridazine

HRID 539807Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]2=[N:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=3)=[CH:10][N:4]2[N:3]=1.CC1(C)C(C)(C)OB([C:29]2[C:30]([C:35]([F:38])([F:37])[F:36])=[N:31][CH:32]=[CH:33][CH:34]=2)O1.CC([O-])=O.[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O.C(O)CCC>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:8]=[C:5]3[N:4]([CH:10]=2)[N:3]=[C:2]([C:29]2[C:30]([C:35]([F:38])([F:37])[F:36])=[N:31][CH:32]=[CH:33][CH:34]=2)[CH:7]=[CH:6]3)=[CH:12][C:13]=1[N+:18]([O-:20])=[O:19]

Participants

Conditions

Temperature: 90 °C

Procedure

A 500 mL flask is charged with 6-chloro-2-(4-methyl-3-nitro-phenyl)imidazo[2,1-f]pyridazine (10.104 g, 0.035 mol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine (Journal of Organic Chemistry, 2011, 76, 1062) (13.38 g, 0.049 mol), KOAc (6.869 g, 0.07 mol), bis(dibenzylideneacetone)palladium(0) (2.01 g, 3.5 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (3.34 g, 0.007 mol), butanol (112 mL) and water (20 mL). The reaction mixture is heated at 90° C. for 4 hr. The reaction is filtered through celite and washed with EtOAc. The liquid layers are combined, concentrated onto celite and purified by silica gel chromatography (0-75% EtOAc in CH2Cl2) to give the title compound (7.98 g, 60% yield). LCMS (m/z)=400.4 [M+H]+, tR=2.76 min.

Workup

filtrationThe reaction is filtered through celite
washwashed with EtOAc
concentrationconcentrated onto celite
custompurified by silica gel chromatography (0-75% EtOAc in CH2Cl2)

Sources & evidence

ORD record: ord-1cc09979ea154dd3a728a51d1e3b8152
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

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