Morpholine → N-[6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]morpholine-4-carboxamide

HRID 2391504Notes

Reaction equation

HRID 2391504 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:34]=[CH:35][CH:36]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:31]=[CH:32][CH:33]=1)[O:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([NH:22][C:23](=[O:30])OCC(Cl)(Cl)Cl)[N:21]=2)[N:18]=1)=[O:7].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C(N(C(C)C)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CS(C)=O>[F:37][C:2]([F:1])([F:38])[C:3]1[CH:4]=[C:5]([CH:34]=[CH:35][CH:36]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:31]=[CH:32][CH:33]=1)[O:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([NH:22][C:23]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:30])[N:21]=2)[N:18]=1)=[O:7]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 61924TriisopropylamineHCID 516892Sodium BicarbonateHCID 575057352,2,2-Trichloroethyl[6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]carbamate

Product 1

HCID 57505736N-[6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]morpholine-4-carboxamideYield 73.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2,2,2-trichloroethyl [6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]carbamate (140 mg, 0.237 mmol), morpholine (31 mL, 0.356 mmol), N,N-diisopropylpropan-2-amine (123 μL, 0.713 mmol) and dimethyl sulfoxide (10 mL) was heated to 80° C. and the mixture was stirred for 24 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 water and saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) and precipitated from diisopropyl ether to give the title compound (92 mg, 73%) as a pale-green powder.

Workup

  1. temperatureto cool to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and 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 silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  8. customprecipitated from diisopropyl ether

Sources & evidence

ORD record
ord-cbcb5f91d3304aec9dd4fa0c34bf3937
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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