Phenylacetyl chloride → HCID 57505538, compound

HRID 1667984Notes

Reaction equation

HRID 1667984 reaction equation
[C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S-:11][C:12]#[N:13].[K+].[NH2:15][C:16]1[CH:17]=[C:18]([CH:35]=[CH:36][CH:37]=1)[O:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([CH:26]=[C:27]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:28]=2)[N:25]=1>C(#N)C>[C:1]1([CH2:7][C:8]([NH:13][C:12]([NH:15][C:16]2[CH:17]=[C:18]([CH:35]=[CH:36][CH:37]=2)[O:19][C:20]2[CH:21]=[CH:22][C:23]3[N:24]([CH:26]=[C:27]([NH:29][C:30]([CH:32]4[CH2:34][CH2:33]4)=[O:31])[N:28]=3)[N:25]=2)=[S:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505538HCID 57505538, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of phenylacetyl chloride (155 mg, 1.0 mmol) in acetonitrile (20 mL) was added potassium thiocyanate (292 mg, 3.0 mmol), and the mixture was stirred at 60° C. for 3 hr and concentrated under reduced pressure. The residue was diluted with tetrahydrofuran (20 mL). N-[6-(3-Aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (155 mg, 0.50 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was concentrated under reduced pressure, water was added to the residue and the mixture was extracted with ethyl acetate. 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 precipitated from diisopropyl ether to give the title compound (142 mg, yield 58%) as a white solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with tetrahydrofuran (20 mL)
  3. stirringthe mixture was stirred at room temperature for 18 hr
  4. concentrationThe reaction mixture was concentrated under reduced pressure, water
  5. additionwas added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30)
  9. customprecipitated from diisopropyl ether

Sources & evidence

ORD record
ord-ded2d4834ca140b1ae9810a24603f9af
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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