Benzeneacetamide → HCID 23153471, compound

HRID 492803Notes

Reaction equation

HRID 492803 reaction equation
[C:1]1([CH2:7][C:8]([NH2:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)[C:12](Cl)=[O:13].[NH2:17][C:18]1[CH:36]=[CH:35][C:21]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31])[CH:24]=2)=[C:20]([F:37])[CH:19]=1.C(OCC)(=O)C>ClCCCl.CN(C)C=O>[CH3:33][N:32]([CH3:34])[C:30]([NH:29][C:25]1[CH:24]=[C:23]([O:22][C:21]2[CH:35]=[CH:36][C:18]([NH:17][C:12]([NH:10][C:8](=[O:9])[CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[O:13])=[CH:19][C:20]=2[F:37])[CH:28]=[CH:27][N:26]=1)=[O:31]

Participants

7

Reactant 4

HCID 7680BenzeneacetamideHCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 23153283HCID 23153283, compound

Product 1

HCID 23153471HCID 23153471, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

2-Phenylacetamide (126 mg) was dissolved in 1,2-dichloroethane (10 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.101 ml) was added thereto, followed by stirring at 110° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (3 ml) under a nitrogen atmosphere. 4-(4-Amino-2-fluorophenoxy)-2-[(dimethylamino)carbonylamino]pyridine (90 mg) was then added thereto, followed by stirring for 20 min. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, to which ethyl acetate (1.5 ml) was added to precipitate crystals. The crystals were filtered off and dried under aeration to provide the titled compound (36.3 mg, 26%) as white crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue, which
  3. stirringby stirring for 20 min
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:3)
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a residue
  13. customto precipitate crystals
  14. filtrationThe crystals were filtered off
  15. customdried under aeration

Sources & evidence

ORD record
ord-8258d5636444406d82ef7c1c69cfd958
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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