Hydrochloric Acid → HCID 178447098, compound

HRID 1905325Notes

Reaction equation

HRID 1905325 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-].[CH2:90]([O:95][CH2:96][CH:97]([OH:104])[C@@H:98](N)[CH2:99][CH:100]([CH3:102])[CH3:101])[CH2:91][CH:92]([CH3:94])[CH3:93].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(N(CC)CC)C>[CH2:90]([O:95][CH2:96][CH:97]([OH:104])[C@@H:98]([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:13](=[O:14])[CH:12]([CH2:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH2:27][C:28](=[O:38])[NH:29][CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:99][CH:100]([CH3:102])[CH3:101])[CH2:91][CH:92]([CH3:94])[CH3:93]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 516892Sodium BicarbonateHCID 86743184(2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl isoamyl etherHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 178447098HCID 178447098, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 115 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 2 ml of N,N-dimethylformamide were added successively dropwise 0.16 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.04 ml of isoamyl nitrite under ice-cooling, and mixture was stirred. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.11 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 63 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl isoamyl ether and 0.035 ml of triethylamine in 2 ml of N,N-dimethylformamide solution 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 magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water32 8/3/1 by volume) to obtain 51 mg of (2RS, 3S)-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)-propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexyl isoamyl ether as a white powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 16 hours under ice-
  3. temperaturecooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water32 8/3/1 by volume)

Sources & evidence

ORD record
ord-8b86088f0ca041cb94e2e2afe20c7e1e
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

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