Oxalyl chloride → HCID 57505689, compound

HRID 2391454Notes

Reaction equation

HRID 2391454 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:5])[CH3:4])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:41]=[CH:42][C:43]=1[F:44])[O:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]3[CH2:40][CH2:39]3)=[O:37])[N:34]=2)[N:31]=1>O1CCCC1.CN(C)C=O.[OH-].[Na+]>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:21][C:22]1[CH:23]=[C:24]([O:25][C:26]2[CH:27]=[CH:28][C:29]3[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]4[CH2:40][CH2:39]4)=[O:37])[N:34]=3)[N:31]=2)[CH:41]=[CH:42][C:43]=1[F:44])=[O:11])([CH3:4])[CH3:5])#[N:2]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 571495383-(2-Cyanopropan-2-yl)benzoic acidHCID 57505446N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505689HCID 57505689, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (100 mg, 0.55 mmol) in tetrahydrofuran (2.0 mL) were added oxalyl chloride (59 μL, 0.69 mmol) and N,N-dimethylformamide (1 drop), and the mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure, and the residue was dissolved in N-methylpyrrolidone (2 mL). N-[6-(3-Amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (150 mg, 0.46 mmol) was added to the mixture, and the mixture was stirred at room temperature for 10 hr. The reaction mixture was diluted with 1N aqueous sodium hydroxide solution. The mixture was 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=40/60→100/0), and precipitated from ethyl acetate/diisopropyl ether to give the title compound (140 mg, 62%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in N-methylpyrrolidone (2 mL)
  3. stirringthe mixture was stirred at room temperature for 10 hr
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and 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 NH silica gel column chromatography (ethyl acetate/hexane=40/60→100/0)
  10. customprecipitated from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-9e6c11aa683b469d921f3832633b5f24
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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