p-Toluenesulfonic acid → HCID 131717380, compound

HRID 1196728Notes

Reaction equation

HRID 1196728 reaction equation
[NH2:1][C@@H:2]([C:6]([NH:8][C@H:9]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])[CH:3]([CH3:5])[CH3:4].CC1C=CC(S(O)(=O)=O)=CC=1.[NH:35]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:36]([C:39](O)=[O:40])[CH2:37][OH:38].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl.C(Cl)(Cl)Cl.O>[NH:35]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:36]([C:37]([NH:1][C@@H:2]([C:6]([NH:8][C@H:9]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:38])[CH2:39][OH:40]

Participants

10

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10781975HCID 10781975, compound

Product 1

HCID 131717380HCID 131717380, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of DVal-Leu-OBzl.p-TsOH(394 mg), Boc-Ser(164 mg), HOBT.H2O(129 mg) and N-methylmorpholine (88 μl) in dichloromethane(1.6 ml) was added EDCI.HCl (161 mg) under ice cooling. The reaction mixture was stirred at room temperature for 3 h. Saturated NaHCO, (2 ml) was added and the mixture was extracted with dichloromethane(15 ml×3). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by dry column flash chromatography on silica gel(Merck, KIESELGEL 60) with dichloromethane/methanol(50/1) for elution to give a solid. The solid was dissolved in chloroform and precipitated with hexane to give Boc-Ser-DVal-Leu-OBzl(355 mg) as a colorless powder. The tripeptide(330 mg) was dissolved in THF(3.3 ml) and 10% Pd/C(33 mg) was added. The mixture was vigorously stirred at room temperature under an atmosphere of hydrogen(under atmospheric pressure) for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. Saturated NaCl (2 ml) was added to the residue and the mixture was extracted with EtOAc(20 ml×3). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to give a solid. The solid was dissolved in chloroform and reprecipitated with hexane to give Boc-Ser-DVal-Leu(246 mg) as a colorless powder.

Workup

  1. extractionthe mixture was extracted with dichloromethane(15 ml×3)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified
  6. dry with materialby dry column flash chromatography on silica gel(Merck, KIESELGEL 60) with dichloromethane/methanol(50/1)
  7. washfor elution
  8. customto give a solid
  9. customprecipitated with hexane

Sources & evidence

ORD record
ord-02c98ea48db448e2b9a36558ed99139b
Source dataset
uspto-grants-1992_05
Patent number
US05114918

Reaction notes

Loading…