Triethylamine → 5-chloro-thiophene-2-carboxylic acid {(1S,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-2-oxo-cyclopentyl}-amide

HRID 2244689Notes

Reaction equation

HRID 2244689 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[NH:15][C:16]([C@@H:18]1[CH2:22][C@H:21]([NH:23][C:24]([C:26]2[S:27][C:28]([Cl:31])=[CH:29][CH:30]=2)=[O:25])[C@@H:20]([OH:32])[CH2:19]1)=[O:17].C(N(CC)CC)C>CS(C)=O.C(Cl)Cl.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[NH:15][C:16]([C@@H:18]1[CH2:22][C@H:21]([NH:23][C:24]([C:26]2[S:27][C:28]([Cl:31])=[CH:29][CH:30]=2)=[O:25])[C:20](=[O:32])[CH2:19]1)=[O:17]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 16066323HCID 16066323, compound

Product 1

HCID 588264485-chloro-thiophene-2-carboxylic acid {(1S,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-2-oxo-cyclopentyl}-amideYield 71.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21912085Dimethylsulfoxide-dichloromethaneSolvent

Procedure

To a stirred solution of 5-chloro-thiophene-2-carboxylic acid {(1S,2S,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-2-hydroxy-cyclopentyl}-amide (318 mg; example 1C) in DMSO/CH2Cl2 1:1 (6 ml) were added triethylamine (0.73 ml) and SO3-pyridine complex (638 mg). The mixture was stirred overnight at r.t. The clear brown solution was diluted with dichloromethane, washed with 0.5 N HCl, H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 95:5) to give 5-chloro-thiophene-2-carboxylic acid {(1S,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-2-oxo-cyclopentyl}-amide (225 mg) as light yellow amorphous solid. MS 474.1 ([M+H]+).

Workup

  1. washwashed with 0.5 N HCl, H2O and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-3d17ebc285144998ba4f3c86db149717
Source dataset
uspto-grants-2010_03
Patent number
US07678917B2

Reaction notes

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