Hydrochloric Acid → HCID 178447157, compound

HRID 1905319Notes

Reaction equation

HRID 1905319 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-].N[C@@H:91]([CH2:102][CH:103]([CH3:105])[CH3:104])[CH:92]([OH:101])[C:93]([O:95][CH2:96][CH2:97][CH:98]([CH3:100])[CH3:99])=[O:94]>CN(C)C=O.C(N(CC)CC)C>[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]([NH:72][C@@H:91]([CH2:102][CH:103]([CH3:105])[CH3:104])[CH:92]([OH:101])[C:93]([O:95][CH2:96][CH2:97][CH:98]([CH3:99])[CH3:100])=[O:94])=[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

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 56608254isoamyl (2RS,3S)-3-amino-2-hydroxy-5-methylhexanoateHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 178447157HCID 178447157, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 200 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 5 ml of N,N-dimethylformamide were added successively dropwise 0.25 ml of a dry 5.1N-hydrogen chloride in N,N-dimethyformamide solution and 0.07 ml of isoamyl nitrite with stirring at -20° C. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.2 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)-propionyl]-L-histidine azide. The azide solution prepared was added dropwise to 110 mg of isoamyl (2RS,3S)-3-amino-2-hydroxy-5-methylhexanoate and 0.1 ml of triethylamine in 2 ml of dry N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours. 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 dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The pressure was purified by silica gel column chromatography (eluent: chloroform/ethanol=10/1 by volume) to obtain 52 mg of isoamyl (2RS,3S)-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Workup

  1. temperaturecooling
  2. customThe reaction mixture was evaporated under reduced pressure
  3. additiona 5% aqueous sodium bicarbonate solution was added to the residue
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialthe ethyl acetate layer was dried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe pressure was purified by silica gel column chromatography (eluent: chloroform/ethanol=10/1 by volume)

Sources & evidence

ORD record
ord-412eb764db1549d3b0107f8f1c7c0e0c
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

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