Dimethylformamide → HCID 57505514, compound

HRID 1667943Notes

Reaction equation

HRID 1667943 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([C:8]([OH:10])=O)=[N:3]1.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:42]=[CH:43][CH:44]=1)[O:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[C:34]([NH:36][C:37]([CH:39]3[CH2:41][CH2:40]3)=[O:38])[N:35]=2)[N:32]=1.C(N(CC)CC)C>O1CCCC1.O>[CH:39]1([C:37]([NH:36][C:34]2[N:35]=[C:30]3[CH:29]=[CH:28][C:27]([O:26][C:25]4[CH:24]=[C:23]([NH:22][C:8]([C:4]5[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=5)=[O:10])[CH:44]=[CH:43][CH:42]=4)=[N:32][N:31]3[CH:33]=2)=[O:38])[CH2:40][CH2:41]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 5877571,5-dimethyl-1H-pyrazole-3-carboxylic acidHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505514HCID 57505514, compoundYield 42.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 1,5-dimethyl-1H-pyrazole-3-carboxylic acid (109 mg, 0.78 mmol) in tetrahydrofuran (4.0 mL) 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 tetrahydrofuran (2.0 mL) was added dropwise to a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropylcarboxamide (200 mg, 0.65 mmol) and triethylamine (360 μL, 2.59 mmol) in tetrahydrofuran (4.0 mL). After stirring at room temperature for 2 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 purified by silica gel column chromatography (hexane/ethyl acetate=1/4→ethyl acetate) and precipitated from hexane/ethyl acetate to give the title compound (118 mg, 42%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringAfter stirring at room temperature for 2 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. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/4→ethyl acetate)
  9. customprecipitated from hexane/ethyl acetate

Sources & evidence

ORD record
ord-0dbddbb60ccf43479547c80255c1229c
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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