Hydrochloric Acid → N(alpha)-(N(alpha)-(N(alpha)-(tert-butyloxycarbonyl)glutaminyl)-N(1)-formyl-tryptophyl)phenylalanine benzyl ester

HRID 2082222Notes

Reaction equation

HRID 2082222 reaction equation
[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:2]([C:8]([OH:10])=O)[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].Cl.[NH2:19][C@@H:20]([C:33]([NH:35][C@H:36]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:34])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]([CH:31]=[O:32])[CH:23]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.C(Cl)Cl>[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:2]([C:8]([NH:19][C@@H:20]([C:33]([NH:35][C@H:36]([C:44]([O:46][CH2:47][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)=[O:45])[CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:34])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]([CH:31]=[O:32])[CH:23]=1)=[O:10])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 83687L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-HCID 15755292HCID 15755292, compound

Product 1

HCID 130847N(alpha)-(N(alpha)-(N(alpha)-(tert-butyloxycarbonyl)glutaminyl)-N(1)-formyl-tryptophyl)phenylalanine benzyl esterYield 95.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Boc-Gln-OH (2.10 g), HCl.H-D-Trp(CHO)-Phe-OBzl (4.70 g) and HOBT (1.15 g) in a mixed solvent of methylene chloride (60 ml) and DMF (10 ml), was added WSC (1.41 g) under ice cooling. The reaction mixture was stirred for 1.5 hours at the same temperature and for additional 1.5 hours at room temperature and concentrated under reduced pressure. Water was added to the residue and the resulting precipitates were collected and washed successively with water, diluted sodium hydrogencarbonate solution and water. After drying, the crude product (5.84 g) was stirred in hot ethyl acetate (60 ml) in water bath. After cooling, the precipitates were collected by filtration and dried to give Boc-Gln-D-Trp(CHO)-Phe-OBzl (5.70 g).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionWater was added to the residue
  3. customthe resulting precipitates
  4. customwere collected
  5. washwashed successively with water, diluted sodium hydrogencarbonate solution and water
  6. customAfter drying
  7. stirringthe crude product (5.84 g) was stirred in hot ethyl acetate (60 ml) in water bath
  8. temperatureAfter cooling
  9. filtrationthe precipitates were collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-5f39904082c44f63a04a9d201caf1a24
Source dataset
uspto-grants-1993_02
Patent number
US05187156

Reaction notes

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