4-Chlorobutyryl chloride → 4-Chloro-N-{4-[1-(4-chloro-2-methyl-phenyl)-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-propyl]-phenyl}-butyramide

HRID 1617958Notes

Reaction equation

HRID 1617958 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=2[CH3:34])[CH2:16][C:17]([C:19]2[CH:20]=[CH:21][C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:11][CH:10]=1>ClCCl.N1C=CC=CC=1>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=2[CH3:34])[CH2:16][C:17]([C:19]2[CH:20]=[CH:21][C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:11][CH:10]=1)=[O:6]

Participants

5

Reactant 2

HCID 783704-Chlorobutyryl chlorideHCID 666687055-[3-(4-Amino-phenyl)-3-(4-chloro-2-methyl-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one

Product 1

HCID 670156854-Chloro-N-{4-[1-(4-chloro-2-methyl-phenyl)-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-propyl]-phenyl}-butyramide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

In a 10 mL round-bottomed flask 5-[3-(4-amino-phenyl)-3-(4-chloro-2-methyl-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one (example 353, step 1, 100 mg) was dissolved in dichloromethane (1.3 mL) and pyridine (41 mg). Then the reaction mixture was cooled in an icebath and 4-chlorobutyryl chloride (41.6 mg) was added slowly. The icebath was removed and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate. The organic layer was washed 1× with 1 M HCl and 2× with water. The aqueous layers were extracted 2× with ethyl acetate, the combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 20 g, 0% to 10% methanol in dichloromethane) to give the title compound as a light yellow foam, MS (ESI+): m/z=485.3 [M+H]+.

Workup

  1. additionwas added slowly
  2. customThe icebath was removed
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washThe organic layer was washed 1× with 1 M HCl and 2× with water
  5. extractionThe aqueous layers were extracted 2× with ethyl acetate
  6. dry with materialthe combined organic layers were dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 20 g, 0% to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-af18fabc02494e0aa47929be3d97bb92
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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