Water → 1-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

HRID 870620Notes

Reaction equation

HRID 870620 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[C:12]([C:15]1[S:19][C:18](B(O)O)=[CH:17][CH:16]=1)(=[O:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:18]3[S:19][C:15]([C:12](=[O:14])[CH3:13])=[CH:16][CH:17]=3)=[CH:3][N:4]=2)[N:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 866963183-Bromo-6-fluoroimidazo[1,2-b]pyridazine

Product 1

HCID 866963171-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-bromo-6-fluoro-imidazo[1,2-b]pyridazine (620 mg, 2.9 mmol), 5-acetyl-2-thiopheneboronic acid [206551-43-1] (634 mg, 3.7 mmol), potassium carbonate [584-08-7] (792 mg, 5.7 mmol), and bis(triphenylphosphine)palladium(II) dichloride [13965-03-2] (100 mg, 0.1 mmol) was suspended in a microwave reaction vial with a 25% (v/v) solution of water in acetonitrile (4.5 mL) then stirred and irradiated to an internal temperature of 145° C. for 15 minutes. The cooled reaction mixture was diluted with ethyl acetate, filtered, and partitioned between 1N aqueous sodium hydroxide and additional ethyl acetate. The organic extract was flash chromatographed (silica gel, eluted with 20% (v/v) ethyl acetate/hexanes) to provide 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone as 300 mg of yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.63 (s, 3H) 7.00 (d, J=9.35 Hz, 1H) 7.75 (d, J=4.04 Hz, 1H) 7.83 (d, J=4.04 Hz, 1H) 8.13 (dd, J=9.60, 7.07 Hz, 1H) 8.21 (s, 1H). LRMS (ESI) m/z 262.1 [(M+H)]+, calc'd for C12H8FN30S: 261.28.

Workup

  1. customirradiated to an internal temperature of 145° C. for 15 minutes
  2. customThe cooled reaction mixture
  3. filtrationfiltered
  4. custompartitioned between 1N aqueous sodium hydroxide and additional ethyl acetate
  5. extractionThe organic extract
  6. customchromatographed
  7. wash(silica gel, eluted with 20% (v/v) ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-656eccbfdce44c81b3dc64194046e40e
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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