1-Methylpiperazine → 3-(1-cyanocyclopropyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}benzamide

HRID 2391526Notes

Reaction equation

HRID 2391526 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:34])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]5([C:32]#[N:33])[CH2:31][CH2:30]5)[CH:24]=4)[CH:18]=[CH:19][CH:20]=3)=[N:10][N:9]2[CH:35]=1)=[O:4].[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(=O)([O-])O.[Na+]>C(#N)C>[C:32]([C:29]1([C:25]2[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=2)[C:22]([NH:21][C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:11]3[CH:12]=[CH:13][C:8]4[N:9]([CH:35]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:40]5[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]5)[N:7]=4)[N:10]=3)[CH:16]=2)=[O:34])[CH2:31][CH2:30]1)#[N:33]

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 57505753N-[3-({2-[(chloroacetyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 575057543-(1-cyanocyclopropyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}benzamideYield 41%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-[3-({2-[(chloroacetyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-(1-cyanocyclopropyl)benzamide (140 mg, 0.287 mmol), 1-methylpiperazine (1 mL) and acetonitrile (2 mL) was stirred with heating at 80° C. for 4 hr. After the reaction mixture was allowed to cool to room temperature, saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=0/100→100/0) to give the title compound (65 mg, 41%) as a white powder.

Workup

  1. temperatureto cool to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=0/100→100/0)

Sources & evidence

ORD record
ord-748d7d0736e443ef9c46f84e4f208d82
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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