Hydrochloric Acid → HCID 178475067, compound

HRID 2082230Notes

Reaction equation

HRID 2082230 reaction equation
N(C(OC(C)(C)C)=O)[C@H:2]([C:9](N[C@@H](C(N[C@H](C(N(CC1C=CC=CC=1)C)=O)CC1C=CC=CC=1)=O)CC1C2C(=CC=CC=2)N(C=O)C=1)=[O:10])CC1N=CNC=1.C1(OC)C=CC=CC=1.[ClH:62].[NH2:63][C@H:64]([C:71]([NH:73][C@@H:74]([C:87]([NH:89][C@H:90]([C:98]([N:100]([CH2:102][C:103]1[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=1)[CH3:101])=[O:99])[CH2:91][C:92]1[CH:97]=[CH:96][CH:95]=[CH:94][CH:93]=1)=[O:88])[CH2:75][C:76]1[C:84]2[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=2)[N:78]([CH:85]=[O:86])[CH:77]=1)=[O:72])[CH2:65][C:66]1[N:70]=[CH:69][NH:68][CH:67]=1.CC(OC(C)=O)=O>C(Cl)Cl.CN(C=O)C.C(N(CC)CC)C>[NH:63]([C:9]([CH3:2])=[O:10])[C@H:64]([C:71]([NH:73][C@@H:74]([C:87]([NH:89][C@H:90]([C:98]([N:100]([CH2:102][C:103]1[CH:104]=[CH:105][CH:106]=[CH:107][CH:108]=1)[CH3:101])=[O:99])[CH2:91][C:92]1[CH:93]=[CH:94][CH:95]=[CH:96][CH:97]=1)=[O:88])[CH2:75][C:76]1[C:84]2[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=2)[N:78]([CH:85]=[O:86])[CH:77]=1)=[O:72])[CH2:65][C:66]1[N:70]=[CH:69][NH:68][CH:67]=1.[ClH:62]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 7918Acetic Anhydride2×HCID 178482738HCID 178482738, compoundHCID 178482739HCID 178482739, compound

Product 1

HCID 178475067HCID 178475067, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

To an ice-cooled solution of Boc-His-D-Trp(CHO)-Phe-NMeBzl (0.70 g) and anisole (0.7 ml) in methylene chloride (5 ml) was added 4N-HCl/DOX (5 ml). The solution was stirred for an hour at room temperature. After evaporation, the residue was pulverized with diisopropyl ether, filtered, washed with diisopropyl ether and dried to give 2HCl.H-His-D-Trp(CHO)-Phe-NMeBzl. The powder (0.70 g) was dissolved in a mixture of methylene chloride (10 ml) and DMF (1 ml) and ice-cooled. To the solution, triethylamine (0.41 ml) and Ac2O (0.09 ml) were added. After stirring for an hour and twenty minutes, triethylamine (0.12 ml) and Ac2O (0.09 ml) were added and stirred for additional half an hour. The mixture was evaporated and the residue was extracted with ethyl acetate. The organic layer was washed successively with water, 2% hydrochloric acid, water and saturated sodium chloride solution, and dried over magnesium sulfate. After evaporation, the residue was dissolved in DMF (10 ml). To the solution, pyridinium chloride (1.16 g) was added and the mixture was stirred for an hour. After evaporation the residue was solidified with water, filtered, washed with water, and dried. The powder was subjected to column chromatography on silica gel (20 g) and eluted with a mixture of chloroform and methanol (9:1). The fractions containing the object compound were combined and evaporated. The residue was pulverized with diethyl ether and filtered. The powder was dissolved in a mixture of chloroform and methanol. To the solution was added 4N-HCl/DOX (0.25 ml) and evaporated. The residue was pulverized with diethyl ether, filtered, washed with diethyl ether and dried to give Ac-His-D-Trp(CHO)-Phe-NMeBzl.HCl (0.31 g).

Workup

  1. customAfter evaporation
  2. filtrationfiltered
  3. washwashed with diisopropyl ether
  4. customdried
  5. customto give 2HCl
  6. temperaturecooled
  7. stirringAfter stirring for an hour and twenty minutes
  8. stirringstirred for additional half an hour
  9. customThe mixture was evaporated
  10. extractionthe residue was extracted with ethyl acetate
  11. washThe organic layer was washed successively with water, 2% hydrochloric acid, water and saturated sodium chloride solution
  12. dry with materialdried over magnesium sulfate
  13. customAfter evaporation
  14. dissolutionthe residue was dissolved in DMF (10 ml)
  15. additionTo the solution, pyridinium chloride (1.16 g) was added
  16. stirringthe mixture was stirred for an hour
  17. customAfter evaporation the residue
  18. filtrationfiltered
  19. washwashed with water
  20. customdried
  21. washeluted with a mixture of chloroform and methanol (9:1)
  22. additionThe fractions containing the object compound
  23. customevaporated
  24. filtrationfiltered
  25. dissolutionThe powder was dissolved in a mixture of chloroform and methanol
  26. additionTo the solution was added 4N-HCl/
  27. customevaporated
  28. filtrationfiltered
  29. washwashed with diethyl ether
  30. customdried

Sources & evidence

ORD record
ord-f27449b8e5fd4d4bae4c8ccd8df917ac
Source dataset
uspto-grants-1993_02
Patent number
US05187156

Reaction notes

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