Hydrochloric Acid → HCID 178445969, compound

HRID 1905332Notes

Reaction equation

HRID 1905332 reaction equation
C1(CC(CC(=O)NCCC2C=CC=CC=2)C(N(C(=O)[C@H](CC2N=CNC=2)N)N)=O)C2C(=CC=CC=2)C=CC=1.Cl.N(OCCC(C)C)=O.[C:48]1([CH2:58][CH:59]([CH2:75][C:76](=[O:86])[NH:77][CH2:78][CH2:79][C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)[C:60]([NH:62][C@H:63]([C:70]([N:72]=[N+]=[N-])=[O:71])[CH2:64][C:65]2[N:69]=[CH:68][NH:67][CH:66]=2)=[O:61])[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50][CH:49]=1.[N-]=[N+]=[N-].Cl.Cl.[CH2:92]([NH:99][CH2:100][CH:101]([OH:108])[C@@H:102](N)[CH2:103][CH:104]([CH3:106])[CH3:105])[C:93]1[CH:98]=[CH:97][CH:96]=[CH:95][CH:94]=1>CN(C)C=O.C(N(CC)CC)C>[CH2:92]([NH:99][CH2:100][CH:101]([OH:108])[C@@H:102]([NH:72][C:70](=[O:71])[C@H:63]([CH2:64][C:65]1[N:69]=[CH:68][NH:67][CH:66]=1)[NH:62][C:60](=[O:61])[CH:59]([CH2:58][C:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50][CH:49]=1)[CH2:75][C:76](=[O:86])[NH:77][CH2:78][CH2:79][C:80]1[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1)[CH2:103][CH:104]([CH3:105])[CH3:106])[C:93]1[CH:98]=[CH:97][CH:96]=[CH:95][CH:94]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 70395546(3S)-N-benzyl-3-amino-2-hydroxy-5-methylhexylamine dihydrochlorideHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 178445969HCID 178445969, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 66 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 5 ml of dry N,N-dimethylformamide were added successively 0.08 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.02 ml of isoamyl nitrite at -20° C. with stirring, and the mixture was stirred under ice-cooling. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.06 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine azide. The azide solution was added dropwise to a solution of 40 mg of (3S)-N-benzyl-3-amino-2-hydroxy-5-methylhexylamine dihydrochloride and 0.018 ml of triethylamine in 2 ml of dry N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. The reaction mixture was evaporated under reduced pressure, and a 5% aqueous sodium bicarbonate solution was added to the residue. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=15/1 by volume) to obtain 33 mg of (2RS, 3S)-N-benzyl-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexylamine as a white powder.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 16 hours under ice-
  4. temperaturecooling
  5. customThe reaction mixture was evaporated under reduced pressure
  6. additiona 5% aqueous sodium bicarbonate solution was added to the residue
  7. extractionThe mixture was extracted with ethyl acetate
  8. washthe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customevaporated under reduced pressure
  11. customThe residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=15/1 by volume)

Sources & evidence

ORD record
ord-619ba144968f4e4aab58f014143175fa
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

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