1,2-Dichloroethane → N-(N-Acetyl-tyrosinyl-valinyl-(4-phenoxyprolinyl))-3-amino-4-oxobutanoic acid

HRID 1182517Notes

Reaction equation

HRID 1182517 reaction equation
[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].CO[C:26](=[O:39])[C@@H:27]1[CH2:31][CH:30]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29][NH:28]1.C([N:43]([CH:46]([CH3:48])[CH3:47])CC)(C)C.C1C=CC2N([OH:58])N=NC=2C=1.C(Cl)CCl.[C:63]([O:66]CC)(=[O:65])C>CN(C)C=O.ClCCl>[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([N:28]1[CH2:29][CH:30]([O:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:31][C@H:27]1[C:26]([NH:43][CH:46]([CH:47]=[O:58])[CH2:48][C:63]([OH:66])=[O:65])=[O:39])=[O:23])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 22875497N-Acetyl-tyrosinyl-valineHCID 545742204-Phenoxyproline methyl ester

Product 1

HCID 22875502N-(N-Acetyl-tyrosinyl-valinyl-(4-phenoxyprolinyl))-3-amino-4-oxobutanoic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-Acetyl-tyrosinyl-valine (0.524 g, 1.63 mmol) and 4-phenoxyproline methyl ester (0.381 g, 1.48 mmol) were dissolved in 4 ml each of dimethylformamide and dichloromethane and cooled to 0° C. To the cooled solution was added diisopropylethylamine (258 ul, 1.86 mmol), HOBT (0.24 g, 1.78 mmol), and EDC (0.37 g, 1.92 mmol) and the reaction was stirred for 18 hrs. The mixture was diluted with 400 ml of ethyl acetate and washed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water. The organic layer was concentrated to give a residue that was purified by flash chromatography (SiO2) eluting with 94:6:1 (CH2Cl2:i-PrOH:Pyridine) to afford 360 mg of the title compound.

Workup

  1. washwashed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water
  2. concentrationThe organic layer was concentrated
  3. customto give a residue that
  4. customwas purified by flash chromatography (SiO2)
  5. washeluting with 94:6:1 (CH2Cl2:i-PrOH:Pyridine)

Sources & evidence

ORD record
ord-22fcbc29b857410f92f04fa854102905
Source dataset
uspto-grants-2007_10
Patent number
US07288624B2

Reaction notes

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