Oxalyl chloride → 1,3-dimethyl-N-{2-methyl-5-[(2-{[(1-methylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1H-pyrazole-5-carboxamide

HRID 1663905

Reaction equation

HRID 1663905 reaction equation
[CH3:1][C:2]1([C:5]([OH:7])=O)[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:15][C:16]1[N:17]=[C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:26]=[CH:27][C:28]([CH3:41])=[C:29]([NH:31][C:32]([C:34]4[N:38]([CH3:39])[N:37]=[C:36]([CH3:40])[CH:35]=4)=[O:33])[CH:30]=3)=[N:20][N:19]2[CH:42]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN(C)C(=O)C.C(OCC)(=O)C.O1CCCC1>[CH3:39][N:38]1[C:34]([C:32]([NH:31][C:29]2[CH:30]=[C:25]([O:24][C:21]3[CH:22]=[CH:23][C:18]4[N:19]([CH:42]=[C:16]([NH:15][C:5]([C:2]5([CH3:1])[CH2:4][CH2:3]5)=[O:7])[N:17]=4)[N:20]=3)[CH:26]=[CH:27][C:28]=2[CH3:41])=[O:33])=[CH:35][C:36]([CH3:40])=[N:37]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 813261-Methylcyclopropanecarboxylic acidHCID 516892Sodium BicarbonateHCID 57505635N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride

Product 1

HCID 575056421,3-dimethyl-N-{2-methyl-5-[(2-{[(1-methylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1H-pyrazole-5-carboxamideYield 74%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

To a solution of 1-methylcyclopropanecarboxylic acid (97 mg, 0.97 mmol) in tetrahydrofuran (1.5 mL) were added N,N-dimethylformamide (1 drop) and oxalyl chloride (83 μL, 0.97 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-methylphenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride (200 mg, 0.48 mmol) in N,N-dimethylacetamide (5 mL), and the mixture was stirred at room temperature for 1 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the mixture, 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→100/0) to give the title compound (105 mg, 74%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hr
  2. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4)
  3. washCombined organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltrated
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→100/0)

Sources & evidence

ORD record
ord-bdb26137f96c4213bc52ae8230ed1035
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Linked notes

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