Water → 2-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)-3-pyrid-4-ylimidazo[1,2-b]pyridazine

HRID 80710

Reaction equation

HRID 80710 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[N:12][N:11]3[CH:23]=2)=[CH:4][CH:3]=1.I[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[N:12][N:11]3[C:23]=2[C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 6094924-IodopyridineHCID 594069602-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 251443712-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)-3-pyrid-4-ylimidazo[1,2-b]pyridazineYield 44.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 0.90 g (2.89 mmol) of 2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine (Synthesis, 2001, 4, 595-600), 0.71 g (3.5 mmol) of 4-iodopyridine, 0.032 g (0.14 mmol) of palladium acetate and 0.48 g (3.5 mmol) of potassium carbonate in 18 mL of dimethylformamide is heated at 135° C. for 18 hours. After cooling, the reaction medium is poured into water and the product is extracted with ethyl acetate. The organic phase is washed with water and dried over sodium sulfate, and the solvent is evaporated off under reduced pressure. The residue is purified on a column of silica gel, eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) to give 0.5 g of crystals after recrystallization from acetonitrile, filtering off and drying under reduced pressure.

Workup

  1. temperatureAfter cooling
  2. extractionthe product is extracted with ethyl acetate
  3. washThe organic phase is washed with water
  4. dry with materialdried over sodium sulfate
  5. customthe solvent is evaporated off under reduced pressure
  6. customThe residue is purified on a column of silica gel
  7. washeluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5)

Sources & evidence

ORD record
ord-f22570aeb09947e6bec8e79b43e87796
Source dataset
uspto-grants-2014_09
Patent number
US08846676B2

Linked notes

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