Triethylamine → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-methylisoxazole-5-carboxamide

HRID 1667924Notes

Reaction equation

HRID 1667924 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:16][C:17]1[CH:18]=[C:19]([CH:36]=[CH:37][CH:38]=1)[O:20][C:21]1[CH:22]=[CH:23][C:24]2[N:25]([CH:27]=[C:28]([NH:30][C:31]([CH:33]3[CH2:35][CH2:34]3)=[O:32])[N:29]=2)[N:26]=1.C(N(CC)CC)C>O1CCCC1.CN(C)C=O.C(=O)([O-])O.[Na+]>[CH:33]1([C:31]([NH:30][C:28]2[N:29]=[C:24]3[CH:23]=[CH:22][C:21]([O:20][C:19]4[CH:18]=[C:17]([NH:16][C:7]([C:5]5[O:4][N:3]=[C:2]([CH3:1])[CH:6]=5)=[O:9])[CH:38]=[CH:37][CH:36]=4)=[N:26][N:25]3[CH:27]=2)=[O:32])[CH2:34][CH2:35]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 8530853-Methylisoxazole-5-carboxylic acidHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505499N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-methylisoxazole-5-carboxamideYield 22.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 3-methylisoxazole-5-carboxylic acid (87 mg, 0.679 mmol) in tetrahydrofuran (2.0 mL) were added N,N-dimethylformamide (1 drop) and oxalyl chloride (75.8 μL, 0.88 mmol), and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (1 mL), and added to a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (140 mg, 0.453 mmol) in tetrahydrofuran (12 mL). Then, triethylamine (138 mg, 1.36 mmol) was added to the mixture, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with saturated aqueous sodium hydrogencarbonate solution, and extracted three times with ethyl acetate, and the 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→80/20) and precipitated from ethyl acetate/hexane to give the title compound (42 mg, 22%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in tetrahydrofuran (1 mL)
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. extractionextracted three times with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→80/20)
  10. customprecipitated from ethyl acetate/hexane

Sources & evidence

ORD record
ord-24ee063152a74757a9d189c02e3f0a46
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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