1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 54403579, compound

HRID 365427Notes

Reaction equation

HRID 365427 reaction equation
C(OC([CH2:8][NH:9][CH:10]([CH2:14][C:15]1[S:16][CH:17]=[CH:18][CH:19]=1)[C:11]([OH:13])=O)=O)(C)(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[Cl:42][C:43]([Cl:59])([Cl:58])[CH2:44][O:45][C:46](=[O:57])[NH:47][CH2:48][CH2:49][CH2:50][CH2:51][C@H:52]([NH2:56])[C:53](=[O:55])[NH2:54]>C(Cl)Cl>[Cl:42][C:43]([Cl:58])([Cl:59])[CH2:44][O:45][C:46](=[O:57])[NH:47][CH2:48][CH2:49][CH2:50][CH2:51][C@@H:52]([C:53](=[O:55])[NH2:54])[NH:56][C:11](=[O:13])[C@H:10]([NH:9][CH3:8])[CH2:14][C:15]1[S:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23290868HCID 23290868, compoundHCID 86755925HCID 86755925, compound

Product 1

HCID 54403579HCID 54403579, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(tert-Butoxycarbonylmethylamino)-3-(2-thienyl)propionic acid (10.07 g; 35 mmole), HOBt (5.72 g; 42 mmole) and EDAC (7.09 g; 37 mmole) were added to methylene chloride (200 ml) and stirred for 15 min. ((5S)-5-amino-5-carbamoylpentyl)carbamic acid 2,2,2-trichloroethyl ester hydrochloride (12.61 g; 35 mmole) was added and the mixture was stirred overnight. Methylene chloride (200 ml) was added and the organic phase was washed with water (200 ml), an aqueous solution of sodium hydrogensulphate (200 ml), an aqueous solution of sodium hydrogencarbonate (200 ml) and water (200 ml). The organic phase was dried (magnesium sulphate) and the solvent was removed in vacuo. The residue was dissolved in a solution of hydrogen chloride in ethyl acetate (3 M; 100 ml) and stirred for 30 min. Diethyl ether and water (500 ml) was added, the phases were separated and the acidic aqueous phase was treated with a solution of sodium carbonate to pH 10. The aqueous phase was extracted with methylene chloride (4×700 ml) and the phases were separated. The organic phase was dried (magnesium sulphate) and the solvent was removed in vacuo to afford 11.0 g of [(5S)-5-carbamoyl-5-((2R)-2-methylamino-3-(2-thienyl)-propionylamino)-pentyl]-carbamic acid 2,2,2-trichloroethyl ester.

Workup

  1. additionwas added
  2. washthe organic phase was washed with water (200 ml)
  3. dry with materialThe organic phase was dried (magnesium sulphate)
  4. customthe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in a solution of hydrogen chloride in ethyl acetate (3 M; 100 ml)
  6. stirringstirred for 30 min
  7. additionDiethyl ether and water (500 ml) was added
  8. customthe phases were separated
  9. additionthe acidic aqueous phase was treated with a solution of sodium carbonate to pH 10
  10. extractionThe aqueous phase was extracted with methylene chloride (4×700 ml)
  11. customthe phases were separated
  12. dry with materialThe organic phase was dried (magnesium sulphate)
  13. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4766d20d900b4a6faf23ca7764a69f21
Source dataset
uspto-grants-2000_10
Patent number
US06127341

Reaction notes

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