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

HRID 1803876Notes

Reaction equation

HRID 1803876 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-d8a62442758e4efe9011422b317e8d40
Source dataset
uspto-grants-2013_01
Patent number
US08354405B2

Reaction notes

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