3-(Trifluoromethyl)benzoyl chloride → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-4-methoxyphenyl]-3-(trifluoromethyl)benzamide

HRID 2391463Notes

Reaction equation

HRID 2391463 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([CH:23]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH:14]=[C:15]([NH:17][C:18]([CH:20]3[CH2:22][CH2:21]3)=[O:19])[N:16]=2)[N:13]=1.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31](Cl)=[O:32]>CN1CCCC1=O.Cl>[CH:20]1([C:18]([NH:17][C:15]2[N:16]=[C:11]3[CH:10]=[CH:9][C:8]([O:7][C:6]4[CH:23]=[C:2]([NH:1][C:31](=[O:32])[C:30]5[CH:34]=[CH:35][CH:36]=[C:28]([C:27]([F:26])([F:37])[F:38])[CH:29]=5)[CH:3]=[CH:4][C:5]=4[O:24][CH3:25])=[N:13][N:12]3[CH:14]=2)=[O:19])[CH2:21][CH2:22]1

Participants

5

Reactant 2

HCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 57505485N-[6-(5-amino-2-methoxyphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505698N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-4-methoxyphenyl]-3-(trifluoromethyl)benzamideYield 80%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of N-[6-(5-amino-2-methoxyphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (150 mg, 0.44 mmol) in N-methylpyrrolidone (6.0 mL) was added 3-(trifluoromethyl)benzoyl chloride (92 mg, 0.44 mmol) under ice-cooling, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate, and the organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=50/50→100/0), and precipitated from ethyl acetate/diisopropyl ether to give the title compound (180 mg, 80%) as a white powder.

Workup

  1. temperaturecooling
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine
  4. dry with materialdried over anhydrous sodium 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=50/50→100/0)
  8. customprecipitated from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-08204fbc6d2e4df1bd9be61e07b59757
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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