Hydrochloric Acid → HCID 178501836, compound

HRID 1905334Notes

Reaction equation

HRID 1905334 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:27][C:28](=[O:38])[NH:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:13](N(C(=O)[C@H](CC2N=CNC=2)N)N)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.N(OCCC(C)C)=O.C1(CC(CC(=O)NCCC2C=CC=CC=2)C([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)C2C(=CC=CC=2)C=CC=1.[N-]=[N+]=[N-].Cl.N[C@@H:92]([CH2:99][CH:100]([CH3:102])[CH3:101])[CH:93]([OH:98])[C:94]([O:96][CH3:97])=[O:95].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(N(CC)CC)C>[C:1]1([CH2:11][CH:12]([CH2:27][C:28](=[O:38])[NH:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:13]([NH:62][C@H:63]([C:70]([NH:72][C@@H:92]([CH2:99][CH:100]([CH3:102])[CH3:101])[CH:93]([OH:98])[C:94]([O:96][CH3:97])=[O:95])=[O:71])[CH2:64][C:65]2[N:69]=[CH:68][NH:67][CH:66]=2)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 516892Sodium BicarbonateHCID 13746619methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochlorideHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 178501836HCID 178501836, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 154 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 4 ml of N,N-dimethylformamide were added successively dropwise 0.19 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.05 ml of isoamyl nitrite at -20° C., and the mixture was stirred. After disapperance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.14 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 a solution of 64 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.09 ml of triethylamine in 2 ml of N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. A 5% aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. 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=10/1 by volume) to obtain 120 mg of methyl (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. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=10/1 by volume)

Sources & evidence

ORD record
ord-9a83ea520e974e79abae9faf86b657ee
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

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