1-Hydroxybenzotriazole → Ethyl 2-(2-(2-imino-4-oxothiazolidin-5-yl)acetamido)-4,5-dimethylthiophene-3-carboxylate

HRID 229451

Reaction equation

HRID 229451 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[C:9]([CH3:12])[S:8][C:7]=1[NH:13][C:14](=[O:20])[CH:15]=[CH:16][C:17](O)=[O:18])=[O:5])[CH3:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:43][C:44]([NH2:46])=[S:45]>CN(C)C=O.C(OCC)(=O)C>[NH2:46][C:44]1[S:45][CH:16]([CH2:15][C:14]([NH:13][C:7]2[S:8][C:9]([CH3:12])=[C:10]([CH3:11])[C:6]=2[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:20])[C:17](=[O:18])[N:43]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 6815482-(3-Carboxy-acryloylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl esterHCID 2723790ThioureaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 2878630Ethyl 2-(2-(2-imino-4-oxothiazolidin-5-yl)acetamido)-4,5-dimethylthiophene-3-carboxylateYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-(3-Carboxy-acryloylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl ester (2.97 g, 10.0 mmol) in 50 mL of N,N-dimethyl-formamide was added N-hydroxy-benzotriazole (1.48 g, 11.0 mmol) and 1-[3-(dimethylamino) propyl]-3-ethyl-carbodiimide hydrochloride (2.88 g, 15.0 mmol). The reaction mixture was stirred at room temperature for 10 minutes and thiourea (0.84 g, 11.0 mmol) was added. The reaction mixture was stirred at room temperature for another 30 minutes and was heated at 60° C. for 12 hours. The reaction mixture was diluted with 250 mL of ethyl acetate and was washed with 100 mL of water and 100 mL of brine. The organic layer was collected, dried over sodium sulfate and concentrated. The residue was load on a 120 g silica gel column and purified by flash chromatography (eluted with a gradient of 0 to 10% ethyl acetate/hexanes). Ethyl 2-{[(2-amino-4-oxo-4,5-dihydro-1,3-thiazol-5-yl) acetyl]amino}-4,5-dimethylthiophene-3-carboxylate (1.80 g, 51% yield) was produced.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for another 30 minutes
  2. temperaturewas heated at 60° C. for 12 hours
  3. washwas washed with 100 mL of water and 100 mL of brine
  4. customThe organic layer was collected
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by flash chromatography (
  8. washeluted with a gradient of 0 to 10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1942ab2eb6dd4fdf969d7c05f33a23f1
Source dataset
uspto-grants-2009_07
Patent number
US07563813B2

Linked notes

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