Sodium Bicarbonate → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-2,5-dimethyl-1,3-oxazole-4-carboxamide

HRID 1663746Notes

Reaction equation

HRID 1663746 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[CH3:24][C:25]1[O:26][C:27]([CH3:33])=[C:28]([C:30](Cl)=[O:31])[N:29]=1.C(OCC)(=O)C.O1CCCC1.C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:30]([C:28]5[N:29]=[C:25]([CH3:24])[O:26][C:27]=5[CH3:33])=[O:31])[CH:23]=[CH:22][CH:21]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 70180202,5-Dimethyl-1,3-oxazole-4-carbonyl chlorideHCID 21939870Tetrahydrofuran ethyl acetateHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 24767978N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-2,5-dimethyl-1,3-oxazole-4-carboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (202 mg, 0.652 mmol) in N,N-dimethylacetamide (4.0 mL) was added a solution of 2,5-dimethyl-1,3-oxazole-4-carbonyl chloride (135 mg, 0.847 mmol) in N,N-dimethylacetamide (1.0 mL), and the mixture was stirred at 0° C. for 1 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the mixture, and the aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran. Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→490/10), and precipitated from ethyl acetate/hexane to give the title compound (213 mg, 76%) as a white powder. melting point 224° C.

Workup

  1. extractionthe aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran
  2. washCombined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→490/10)
  7. customprecipitated from ethyl acetate/hexane

Sources & evidence

ORD record
ord-5cbe36e197e04d7b88872db33303281c
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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