Oxalyl chloride → HCID 57505619, compound

HRID 1668071Notes

Reaction equation

HRID 1668071 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=[N:3]1.C(Cl)(=O)C(Cl)=O.[NH2:16][C:17]1[CH:18]=[C:19]([CH:36]=[CH:37][C:38]=1[CH3:39])[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(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN(C)C(=O)C.C(OCC)(=O)C.O1CCCC1>[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:36]=[CH:37][C:38]([CH3:39])=[C:17]([NH:16][C:7]([C:6]5[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=5)=[O:9])[CH:18]=4)=[N:26][N:25]3[CH:27]=2)=[O:32])[CH2:34][CH2:35]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 6431581-methyl-1H-pyrazole-5-carboxylic acidHCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505619HCID 57505619, compoundYield 83%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

To a solution of 1-methyl-1H-pyrazole-5-carboxylic acid (106 mg, 0.84 mmol) in tetrahydrofuran (5 mL) were added N,N-dimethylformamide (1 drop), oxalyl chloride (91 μL, 1.0 mmol), and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, and the obtained 1-methyl-1H-pyrazole-5-carbonylchloride was dissolved in N,N-dimethylacetamide (2 mL). This was added to a solution of N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (210 mg, 0.65 mmol) in N,N-dimethylacetamide (5 mL), and the mixture was stirred at room temperature for 30 min. To the mixture were added ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution, and the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4). Combined organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→90/10) to give the title compound (230 mg, 83%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe obtained 1-methyl-1H-pyrazole-5-carbonylchloride was dissolved in N,N-dimethylacetamide (2 mL)
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4)
  5. washCombined organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→90/10)

Sources & evidence

ORD record
ord-d7c6d34bbca94b35b326a4ecd4015d5f
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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