1-(4-Aminophenyl)-1H-pyridin-2-one → 5-chloro-thiophene-2-carboxylic acid ((R)-1-{2-[4-(2-oxo-pyridin-1-yl)-phenylamino]-acetyl}-pyrrolidin-3-yl)-amide

HRID 1162614Notes

Reaction equation

HRID 1162614 reaction equation
Br[CH2:2][C:3]([N:5]1[CH2:9][CH2:8][C@@H:7]([NH:10][C:11]([C:13]2[S:14][C:15]([Cl:18])=[CH:16][CH:17]=2)=[O:12])[CH2:6]1)=[O:4].[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]2=[O:32])=[CH:22][CH:21]=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[O:32]=[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][N:26]1[C:23]1[CH:22]=[CH:21][C:20]([NH:19][CH2:2][C:3]([N:5]2[CH2:9][CH2:8][C@@H:7]([NH:10][C:11]([C:13]3[S:14][C:15]([Cl:18])=[CH:16][CH:17]=3)=[O:12])[CH2:6]2)=[O:4])=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 115356951-(4-Aminophenyl)-1H-pyridin-2-oneHCID 587482465-chloro-thiophene-2-carboxylic acid [(R)-1-(2-bromo-acetyl)-pyrrolidin-3-yl]-amide

Product 1

HCID 587482155-chloro-thiophene-2-carboxylic acid ((R)-1-{2-[4-(2-oxo-pyridin-1-yl)-phenylamino]-acetyl}-pyrrolidin-3-yl)-amideYield 26.7%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

7.2 A solution of 250 mg 5-chloro-thiophene-2-carboxylic acid [(R)-1-(2-bromo-acetyl)-pyrrolidin-3-yl]-amide in 2 ml DMF was treated with 110 mg 1-(4-amino-phenyl)-1H-pyridin-2-one (CAS 13143-47-0), 0.12 ml TEA and 110 mg tetrabutylammonium iodide. The reaction mixture was stirred at r.t. for 2 days, then quenched with water and extracted with EtOAc. The organic layer was washed with water, dried over MgSO4 and filtrated. The crude product was purified by chromatography (silica gel; gradient: CH2Cl2 to CH2Cl2/MeOH 95:5) to give 72 mg 5-chloro-thiophene-2-carboxylic acid ((R)-1-{2-[4-(2-oxo-pyridin-1-yl)-phenylamino]-acetyl}-pyrrolidin-3-yl)-amide. MS 457.5 ([M+H]+)

Workup

  1. customquenched with water
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltrated
  6. customThe crude product was purified by chromatography (silica gel; gradient: CH2Cl2 to CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-0f867f1b9786411aa1c4481c766ff3f5
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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