Hydrochloric Acid → HCID 178496810, compound

HRID 1905322Notes

Reaction equation

HRID 1905322 reaction equation
C1(CC(CC(=O)NCCC2C=CC=CC=2)C([N:15](C(=O)[C@H](CC2N=CNC=2)N)N)=O)C2C(=CC=CC=2)C=CC=1.Cl.[C:40]1([CH2:50][CH:51]([CH2:67][C:68](=[O:78])[NH:69][CH2:70][CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[C:52]([NH:54][C@H:55]([C:62](N=[N+]=[N-])=[O:63])[CH2:56][C:57]2[N:61]=[CH:60][NH:59][CH:58]=2)=[O:53])[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][CH:41]=1.[N-]=[N+]=[N-].Cl.[CH3:83][O:84][CH2:85][CH:86]([OH:93])[C@@H:87](N)[CH2:88][CH:89]([CH3:91])[CH3:90]>CN(C)C=O.N(OCCC(C)C)=O.C(N(CC)CC)C>[CH3:83][O:84][CH:85]([NH2:15])[CH:86]([OH:93])[C@@H:87]([C:62](=[O:63])[C@H:55]([CH2:56][C:57]1[N:61]=[CH:60][NH:59][CH:58]=1)[NH:54][C:52](=[O:53])[CH:51]([CH2:50][C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][CH:41]=1)[CH2:67][C:68](=[O:78])[NH:69][CH2:70][CH2:71][C:72]1[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=1)[CH2:88][CH:89]([CH3:91])[CH3:90]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 33558AzideHCID 86743183(2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl methyl ether hydrochlorideHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 178496810HCID 178496810, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent3×HCID 8053Isoamyl NitriteSolventHCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 130 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 6 ml of dry 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, and the mixture was stirred. After disappearance 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 drowise to a solution of 52 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl methyl ether hydrochloride and 0.05 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 preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water32 8/3/1 by volume) to obtain 55 mg of (2RS, 3S)-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}-amino-2-hydroxy-5-methylhexyl methyl ether as a white powder.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. customThe reaction mixture was evaporated under reduced pressure
  4. additiona 5% aqueous sodium bicarbonate solution was added to the residue
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customevaporated under reduced pressure
  9. 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-5f5699e2d4d2410ab1ce600b31969d1f
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

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