1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67771702, compound

HRID 1957029Notes

Reaction equation

HRID 1957029 reaction equation
CC1C=C(C=C(C)C=1)C([N:7](C)[C@:8](C)([C:21]([OH:23])=O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:20]=[CH:19][S:18][CH:17]=2)=[CH:12][CH:11]=1)=O.Cl.[CH3:31][O:32][C:33](=[O:46])[C@H:34]([CH2:36][C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[NH:39][CH:38]=1)[NH2:35].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C.C(OCC)(=O)C>[CH3:31][O:32][C:33](=[O:46])[C@H:34]([CH2:36][C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[NH:39][CH:38]=1)[NH:35][C:21](=[O:23])[C@H:8]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:20]=[CH:19][S:18][CH:17]=2)=[CH:14][CH:15]=1)[NH2:7]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2734891Methyl tryptophanate hydrochlorideHCID 67674953HCID 67674953, compound

Product 1

HCID 67771702HCID 67771702, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(3,5-dimethylbenzoyl)-N-methyl-2-methyl-3-[4-(3-thienyl)phenyl]alanine (135 mg, 0.33 mmol) in DMF are successively added tryptophan methyl ester hydrochloride (110 ml, 0.43 mmol), 1-Hydroxybenzotriazole (58 mg, 0.43 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (5.46M solution) 79μ, 0.43 mmol) at 0° C. under nitrogen atomosphere. The reaction mixture is allowed to stir at 0° C. for 2 h, then at room temperature overnight. The mixture is diluted with ethyl acetate and washed with 10% citric acid twice. The organic layer is dried over magnesium sulfate and concentrated in vacuo. The residue is chromatographed on silica with hexane/ethyl acetate (1:1) to give (D,L)-isomer (55 mg) and (L,L)-isomer (80 mg: including 15% of (D,L)-isomer) (total 67%) of 3-[4-(3-thienyl)phenyl]alanyl-tryptophan methyl ester. Hydrolysis of (D,L)-isomer (55 mg, 0.09 mmol) with lithium hydroxide hydrate (6 mg, 0.14 mmol) affords N-(3,5-Dimethylbenzoyl)-N-methyl-(D)-2-methyl-3-[4-(3-thienyl)phenyl)-alanyl-(L)-tryptophan FAB-MS m/e 592 (M-H)+.

Workup

  1. customat 0° C.
  2. customat room temperature
  3. customovernight
  4. washwashed with 10% citric acid twice
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue is chromatographed on silica with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-3e8761c381a5486d960bfcb33a9a8cb9
Source dataset
uspto-grants-1998_07
Patent number
US05780498

Reaction notes

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