Dimethylformamide → HCID 57505588, compound

HRID 1663850Notes

Reaction equation

HRID 1663850 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([C:8]([OH:10])=O)=[C:3]1[CH3:11].CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[CH:25]=[C:26]([CH:43]=[CH:44][C:45]=1[CH3:46])[O:27][C:28]1[CH:29]=[CH:30][C:31]2[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]3[CH2:42][CH2:41]3)=[O:39])[N:36]=2)[N:33]=1.C(N(CC)CC)C>O1CCCC1.CN(C)C(=O)C.O>[CH:40]1([C:38]([NH:37][C:35]2[N:36]=[C:31]3[CH:30]=[CH:29][C:28]([O:27][C:26]4[CH:43]=[CH:44][C:45]([CH3:46])=[C:24]([NH:23][C:8]([C:4]5[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[C:3]=5[CH3:11])=[O:10])[CH:25]=4)=[N:33][N:32]3[CH:34]=2)=[O:39])[CH2:41][CH2:42]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 7364911,2,5-trimethyl-1H-pyrrole-3-carboxylic acidHCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505588HCID 57505588, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 1,2,5-trimethylpyrrole-3-carboxylic acid (142 mg, 0.93 mmol) in tetrahydrofuran (4.0 mL) were added N,N-dimethylformamide (20 μL, 0.26 mmol) and oxalyl chloride (108 μL, 1.24 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol) and triethylamine (259 μL, 1.86 mmol) in N,N-dimethylacetamide (4.0 mL), and the mixture was stirred at 50° C. for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/3→ethyl acetate alone), washed with hexane/ethyl acetate and filtrated to give the title compound (68 mg, 24%) as a white powder.

Workup

  1. stirringthe mixture was stirred at 50° C. for 16 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/3→ethyl acetate alone),
  8. washwashed with hexane/ethyl acetate
  9. filtrationfiltrated

Sources & evidence

ORD record
ord-aa04f6b24a69409ebe674516e052f65e
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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