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

HRID 80709

Reaction equation

HRID 80709 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[C:23]=2[CH:24]2[CH:29]=[CH:28][N:27](C(OCC)=O)[CH:26]=[CH:25]2)=[CH:4][CH:3]=1.C1(Cl)C(Cl)=C(Cl)C(=O)C(=O)C=1Cl.[OH-].[Na+]>C1(C)C=CC=CC=1>[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:24]2[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 73252o-ChloranilHCID 59406952ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate

Product 1

HCID 251443712-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)-3-pyrid-4-ylimidazo[1,2-b]pyridazineYield 56%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a suspension of 1.00 g (2.16 mmol) of ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate in 35 mL of toluene is added a solution of 0.65 g (2.6 mmol) of ortho-chloranil in 6 mL of toluene. After reaction for 6 hours, 60 mL of 1N sodium hydroxide are added and the product is extracted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the solvent is evaporated off under reduced pressure. 1.2 g of solid are thus recovered, and are purified on a column of silica gel, eluting with a stepwise gradient of 3% to 15% methanol in dichloromethane. The product obtained is washed with diisopropyl ether and recrystallized from isopropyl alcohol to give 0.47 g of crystals after filtering off and drying under reduced pressure.

Workup

  1. customAfter reaction for 6 hours
  2. extractionthe product is extracted with ethyl acetate
  3. washThe organic phase is washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. customthe solvent is evaporated off under reduced pressure
  6. custom1.2 g of solid are thus recovered
  7. customare purified on a column of silica gel
  8. washeluting with a stepwise gradient of 3% to 15% methanol in dichloromethane
  9. customThe product obtained
  10. washis washed with diisopropyl ether
  11. customrecrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-f8c9fd7bfe3f4d94a1d0ea277b3410ea
Source dataset
uspto-grants-2014_09
Patent number
US08846676B2

Linked notes

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