Oxalyl chloride → HCID 24767985, compound

HRID 1663799Notes

Reaction equation

HRID 1663799 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](O)=[O:8])[C:4]([CH3:10])=[N:3]1.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[CH:19]=[C:20]([CH:37]=[CH:38][C:39]=1[F:40])[O:21][C:22]1[CH:23]=[CH:24][C:25]2[N:26]([CH:28]=[C:29]([NH:31][C:32]([CH:34]3[CH2:36][CH2:35]3)=[O:33])[N:30]=2)[N:27]=1>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[CH:34]1([C:32]([NH:31][C:29]2[N:30]=[C:25]3[CH:24]=[CH:23][C:22]([O:21][C:20]4[CH:37]=[CH:38][C:39]([F:40])=[C:18]([NH:17][C:7]([C:5]5[C:4]([CH3:10])=[N:3][N:2]([CH3:1])[CH:6]=5)=[O:8])[CH:19]=4)=[N:27][N:26]3[CH:28]=2)=[O:33])[CH2:35][CH2:36]1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 12733041,3-dimethyl-1H-pyrazole-4-carboxylic acidHCID 57505446N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 24767985HCID 24767985, compoundYield 39.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,3-dimethyl-1H-pyrazole-4-carboxylic acid (140 mg, 1.0 mmol) and N,N-dimethylformamide (2 drops) in tetrahydrofuran (10 mL) was added oxalyl chloride (0.171 mL, 2.0 mmol) with stirring under ice-cooling, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in N-methylpyrrolidone (5 mL) with stirring under ice-cooling, N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (164 mg, 0.50 mmol) was added, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was diluted with ethyl acetate (80 mL), and washed with 1N aqueous sodium hydroxide solution (10 mL) and water (10 mL×3). The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30) and recrystallized from ethyl acetate to give the title compound (88 mg, yield 39%) as a white solid. melting point 205° C.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 2 hr
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in N-methylpyrrolidone (5 mL)
  5. stirringwith stirring under ice-
  6. temperaturecooling
  7. stirringthe mixture was stirred at room temperature for 18 hr
  8. washwashed with 1N aqueous sodium hydroxide solution (10 mL) and water (10 mL×3)
  9. concentrationThe organic layer was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30)
  11. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-0ba4b75e01a94738b1e8192761e739c7
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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