1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 70291844, compound

HRID 365428Notes

Reaction equation

HRID 365428 reaction equation
C(OC(C[NH:9][C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11]([OH:13])=O)=O)(C)(C)C.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[Cl:46][C:47]([Cl:74])([Cl:73])[CH2:48][O:49][C:50](=[O:72])[NH:51][CH2:52][CH2:53][CH2:54][CH2:55][C@@H:56]([C:69](=[O:71])[NH2:70])[NH:57][C:58](=[O:68])[C@H:59]([NH:66][CH3:67])[CH2:60][C:61]1[S:62][CH:63]=[CH:64][CH:65]=1>C(Cl)Cl>[Cl:74][C:47]([Cl:46])([Cl:73])[CH2:48][O:49][C:50](=[O:72])[NH:51][CH2:52][CH2:53][CH2:54][CH2:55][C@H:56]([NH:57][C:58](=[O:68])[C@H:59]([NH:66][CH2:67][C:11](=[O:13])[C@H:10]([NH2:9])[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[CH2:60][C:61]1[S:62][CH:63]=[CH:64][CH:65]=1)[C:69](=[O:71])[NH2:70]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 54403579HCID 54403579, compoundHCID 54532855HCID 54532855, compound

Product 1

HCID 70291844HCID 70291844, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2R)-2-(tert-Butoxycarbonylmethylamino)-3-(2-napthyl)propionic acid (5.00 g; 15.8 mmole), HOAt (2.35 g; 17 mmole) and EDAC (3.03 g; 15.8 mmole) were added to methylene chloride (200 ml) and stirred for 15 min. [(5S)-5-carbamoyl-5-((2R)-2-methylamino-3-(2-thienyl)propionylamino)pentyl]carbamic acid 2,2,2-trichloroethyl ester (7.01 g; 14.5 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 mixture of trifluoroacetic acid (30 ml) and methylene chloride (70 ml) and stirred for 15 min. Water (150 ml) and sodium hydrogencarbonate were added to neutral pH, the phases were separated and the aqueous phase was extracted with methylene chloride (2×100 ml) and the phases were separated. The combined organic phase were dried (magnesium sulphate) and the solvent was removed in vacuo and the residue was chromatographed on silica using a mixture of aqueous ammonia in water (25%), ethanol and methylene chloride (0.7:9.3:90) as eluent to afford 6.3 g of ((5S)-5-{(2R)-2-[((2R)-2-amino-3-(2-naphthyl)propionyl)methylamino]-3-(2-thienyl)propionylamino}-5-carbamoylpentyl)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 mixture of trifluoroacetic acid (30 ml) and methylene chloride (70 ml)
  6. stirringstirred for 15 min
  7. additionWater (150 ml) and sodium hydrogencarbonate were added to neutral pH
  8. customthe phases were separated
  9. extractionthe aqueous phase was extracted with methylene chloride (2×100 ml)
  10. customthe phases were separated
  11. dry with materialThe combined organic phase were dried (magnesium sulphate)
  12. customthe solvent was removed in vacuo
  13. customthe residue was chromatographed on silica using
  14. additiona mixture of aqueous ammonia in water (25%), ethanol and methylene chloride (0.7:9.3:90) as eluent

Sources & evidence

ORD record
ord-d1f05fedca9e403e891204acdab8b305
Source dataset
uspto-grants-2000_10
Patent number
US06127341

Reaction notes

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