Phenylacetyl chloride → HCID 57505780, compound

HRID 1664059Notes

Reaction equation

HRID 1664059 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+].C1(C)C=CC=CC=1.C(O)C.[NH2:25][C:26]1[CH:47]=[CH:46][C:29]([O:30][C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41]([CH:43]4[CH2:45][CH2:44]4)=[O:42])[N:39]=3)[N:36]=2)=[CH:28][CH:27]=1>C(#N)C.[Cl-].[Na+].O>[C:1]1([CH2:7][C:8]([NH:13][C:12]([NH:25][C:26]2[CH:47]=[CH:46][C:29]([O:30][C:31]3[CH:32]=[CH:33][C:34]4[N:35]([CH:37]=[C:38]([NH:40][C:41]([CH:43]5[CH2:44][CH2:45]5)=[O:42])[N:39]=4)[N:36]=3)=[CH:28][CH:27]=2)=[S:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 21863594Toluene ethanolHCID 57505463N-[6-(4-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505780HCID 57505780, compoundYield 51.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of phenylacetyl chloride (342 μL, 2.59 mmol) in acetonitrile (8.0 mL) was added potassium thiocyanate (0.31 g, 3.23 mmol), and the mixture was stirred at 50° C. for 1 hr. After cooling the mixture to room temperature, the solvent was evaporated under reduced pressure. Saturated brine was added to the residue, and the mixture was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Toluene/ethanol (2.0 mL/2.0 mL) was added to the residue, N-[6-(4-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.65 mmol) was added to the mixture, and the mixture was stirred at room temperature for 1 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/3) to give the title compound (164 mg, 51%) as white crystals.

Workup

  1. temperatureAfter cooling the mixture to room temperature
  2. customthe solvent was evaporated under reduced pressure
  3. additionSaturated brine was added to the residue
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. additionwas added to the mixture
  8. stirringthe mixture was stirred at room temperature for 1 hr
  9. extractionthe mixture was extracted with ethyl acetate
  10. washwashed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/3)

Sources & evidence

ORD record
ord-d4624adcfa6f4ae498327458eb7bb304
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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