Dimethylformamide → N-(3-{[2-(acetylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1667934

Reaction equation

HRID 1667934 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][C:4]([CH3:10])=[N:3]1.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:40]=[CH:41][CH:42]=1)[O:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[C:34]([NH:36][C:37](=[O:39])[CH3:38])[N:35]=2)[N:32]=1>O1CCCC1.CN(C)C(=O)C.O>[C:37]([NH:36][C:34]1[N:35]=[C:30]2[CH:29]=[CH:28][C:27]([O:26][C:25]3[CH:24]=[C:23]([NH:22][C:7]([C:6]4[N:2]([CH3:1])[N:3]=[C:4]([CH3:10])[CH:5]=4)=[O:9])[CH:42]=[CH:41][CH:40]=3)=[N:32][N:31]2[CH:33]=1)(=[O:39])[CH3:38]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 5877211,3-Dimethyl-1H-pyrazole-5-carboxylic acidHCID 57441053N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide

Product 1

HCID 57505506N-(3-{[2-(acetylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 67%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a solution (4.0 mL) of 1,3-dimethyl-1H-pyrazole-5-carboxylic acid (109 mg, 0.85 mmol) in tetrahydrofuran were added N,N-dimethylformamide (30 μL, 0.39 mmol) and oxalyl chloride (135 μL, 1.55 mmol), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and a solution of the residue in N,N-dimethylacetamide (2.0 mL) was added dropwise to a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide (200 mg, 0.71 mmol) in N,N-dimethylacetamide (2.0 mL). After the reaction mixture was stirred at room temperature for 1 hr, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was washed with ethyl acetate to give the title compound (182 mg, 67%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringAfter the reaction mixture was stirred at room temperature for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. washthe residue was washed with ethyl acetate

Sources & evidence

ORD record
ord-e85e510461ab4c8f880627377fd5d148
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Linked notes

Loading…