Phenylacetyl chloride → HCID 58158537, compound

HRID 2095882Notes

Reaction equation

HRID 2095882 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+].C(=O)([O-])O.[Na+].[NH2:20][C:21]1[CH:42]=[CH:41][C:24]([O:25][C:26]2[CH:27]=[CH:28][C:29]3[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]4[CH2:40][CH2:39]4)=[O:37])[N:34]=3)[CH:31]=2)=[CH:23][CH:22]=1>C(#N)C.C1(C)C=CC=CC=1.C(O)C>[C:1]1([CH2:7][C:8]([NH:13][C:12]([NH:20][C:21]2[CH:42]=[CH:41][C:24]([O:25][C:26]3[CH:27]=[CH:28][C:29]4[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]5[CH2:39][CH2:40]5)=[O:37])[N:34]=4)[CH:31]=3)=[CH:23][CH:22]=2)=[S:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 516892Sodium Bicarbonate2×HCID 58158625N-[6-(4-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158537HCID 58158537, compoundYield 31.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of phenylacetyl chloride (422 mg, 2.59 mmol) in acetonitrile (8 mL) was added potassium thiocyanate (317 mg, 3.24 mmol), and the mixture was stirred at 50° C. for 1 hr. The reaction solution was cooled to room temperature, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was dissolved in toluene (2 mL)/ethanol (2 mL), N-[6-(4-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 649 μmol) was added, and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with 1N aqueous sodium hydroxide solution, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) and recrystallized from ethanol/water to give the title compound (98 mg, 31%) as a pale-yellow powder.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. additionwas added
  7. stirringthe mixture was stirred at room temperature for 1 hr
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with 1N aqueous sodium hydroxide solution, water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated
  12. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  13. customrecrystallized from ethanol/water

Sources & evidence

ORD record
ord-2eb670ed2ee14ee2848f6038cc05843e
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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