Chloroacetamide → 3-Amino-7-carboxymethyl-4-thiophen-2-yl-6,7-dihydro-5H-cyclopenta[b]thieno[3,2-e]pyridine-2-carboxylic acid amide

HRID 2375366Notes

Reaction equation

HRID 2375366 reaction equation
[C:1]([C:3](=[CH:7][C:8]1[S:9][CH:10]=[CH:11][CH:12]=1)[C:4]([NH2:6])=[S:5])#[N:2].O=[C:14]1[CH2:18][CH2:17][CH2:16][CH:15]1[CH2:19][C:20]([OH:22])=[O:21].CN1CCOCC1.Cl[CH2:31][C:32]([NH2:34])=[O:33].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[NH2:2][C:1]1[C:3]2[C:7]([C:8]3[S:9][CH:10]=[CH:11][CH:12]=3)=[C:18]3[CH2:17][CH2:16][CH:15]([CH2:19][C:20]([OH:22])=[O:21])[C:14]3=[N:6][C:4]=2[S:5][C:31]=1[C:32]([NH2:34])=[O:33]

Participants

7

Reactant 5

HCID 6580ChloroacetamideHCID 79724-MethylmorpholineHCID 11430Potassium CarbonateHCID 27298552-Cyano-3-thiophen-2-yl-thioacrylamideHCID 35699832-(2-oxocyclopentyl)acetic Acid

Product 1

HCID 598548773-Amino-7-carboxymethyl-4-thiophen-2-yl-6,7-dihydro-5H-cyclopenta[b]thieno[3,2-e]pyridine-2-carboxylic acid amideYield 31%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of 2-cyano-3-thiophen-2-yl-thioacrylamide (6.3 g, 33 mmol), 2-oxocyclopentaneacetic acid (4.6 g, 33 mmol) in 70 ml of ethanol was added N-methylmorpholine (6.6 g, 65 mmol). The resulting mixture was refluxed overnight, then 2-chloroacetamide (6.1 g, 65 mmol) and anhydrous potassium carbonate (9.0 g, 65 mmol) was added with stirring. The reaction mixture was continued to reflux overnight. The reaction mixture was cooled to room temperature and the solid was filtered and washed with ethanol. The sodium salt of product was dissolved in 100 ml of water and neutralized with 10% hydrochloric acid to pH<6. The precipitate was filtered and washed with water to give 3.7 g (31%) of pure product as a yellow solid. 1H-NMR (300 MHz, DMSO-d6): δ 12.24 (brs, 1H), 7.87 (d, J=5.1 Hz, 1H), 7.27-7.24 (m, 2H), 7.18 (brs, 2H), 5.93 (brs, 2H), 3.55 (m, 1H), 2.94 (dd, J=3.9, 16.2 Hz, 1H), 2.68 (m, 2H), 2.40 (m, 2H), 1.75 (m, 1H). ES MS m/z 374 (M+H)+, 372 (M−H)−.

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. temperatureto reflux overnight
  3. filtrationthe solid was filtered
  4. washwashed with ethanol
  5. dissolutionThe sodium salt of product was dissolved in 100 ml of water and neutralized with 10% hydrochloric acid to pH<6
  6. filtrationThe precipitate was filtered
  7. washwashed with water

Sources & evidence

ORD record
ord-9d4775d427f8496ea98a351c0927bdbf
Source dataset
uspto-grants-2008_12
Patent number
US07465742B2

Reaction notes

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