1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 70094113, compound

HRID 1957036Notes

Reaction equation

HRID 1957036 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:25]=[C:26]([CH3:28])[CH:27]=1)[C:5]([N:7]([CH3:24])[C@H:8]([C:21]([OH:23])=O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[O:20][N:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)=[O:6].Cl.[CH3:30][O:31][C:32](=[O:45])[C@H:33]([CH2:35][C:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[NH:38][CH:37]=1)[NH2:34].OC1C2N=NNC=2C=CC=1.CN(C)CCCN=C=NCC>CN(C)C=O>[CH3:30][O:31][C:32](=[O:45])[C@H:33]([CH2:35][C:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[NH:38][CH:37]=1)[NH:34][C:21](=[O:23])[C@@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[O:20][N:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)[N:7]([C:5](=[O:6])[C:4]1[CH:3]=[C:2]([CH3:1])[CH:27]=[C:26]([CH3:28])[CH:25]=1)[CH3:24]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2734891Methyl tryptophanate hydrochlorideHCID 18663506HCID 18663506, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 70094113HCID 70094113, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At 0° C., N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-alanine (445 mg) is stirred in N,N-dimethylformamide (24 ml) together with (L)-tryptophane methyl ester hydrochloride (400 mg), hydroxybenztriazol (330 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.32 ml) for 1 hour and at ambient temperature over night. After extraction with ethyl acetate and 10% aqueous citric acid the organic phase is washed with 4% aqueous sodium bicarbonate, and with brine, dried and evaporated. Flash chromatography on silica gel (hexane/ethyl acetate 2:1) gives the product as a mixture of diastereoisomers. Separation by medium pressure chromatography on a silica gel column, using ether/dichloromethane (1:1) as solvent gives both [N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-(D)-alanyl]-(L)-tryptophane methyl ester. NMR (CDCl3, 400 MHz) δ [ppm] 8.60 (s), 8.30 (m), 7.70 (m), 7.55 (m), 7.30 (m), 7.10 (m), 6.90 (m), 6.50 (m), 5.85 (s), 5,43 (m), 4.90 (m), 4.33 (m), 3.75 (s), 3.70 (s), 3.35 (m), 3.15 (m), 2.85 (s), 2.57 (s), 2.35 (s), 2.20 (s), 1.93 (s), 1.85 (s).

Workup

  1. extractionAfter extraction with ethyl acetate and 10% aqueous citric acid the organic phase
  2. washis washed with 4% aqueous sodium bicarbonate
  3. dry with materialwith brine, dried
  4. customevaporated
  5. customFlash chromatography on silica gel (hexane/ethyl acetate 2:1) gives the product
  6. additionas a mixture of diastereoisomers
  7. customSeparation by medium pressure chromatography on a silica gel column

Sources & evidence

ORD record
ord-e122dad9dc4240b3938cd123bf586bcd
Source dataset
uspto-grants-1998_07
Patent number
US05780498

Reaction notes

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