Hydrochloric Acid → HCID 178445967, compound

HRID 542374Notes

Reaction equation

HRID 542374 reaction equation
C1(CC(CC(N2CCCCC2)=O)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:45]1([CH2:55][CH:56]([CH2:72][C:73]([N:75]2[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]2)=[O:74])[C:57]([NH:59][C@H:60]([C:67]([N:69]=[N+]=[N-])=[O:68])[CH2:61][C:62]2[N:66]=[CH:65][NH:64][CH:63]=2)=[O:58])[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[CH:47][CH:46]=1.[N-]=[N+]=[N-].Cl.N[C@@H:86]([CH2:95][CH:96]([CH3:98])[CH3:97])[CH:87]([OH:94])[C:88]([O:90][CH:91]([CH3:93])[CH3:92])=[O:89]>CN(C)C=O.C(N(CC)CC)C>[C:45]1([CH2:55][CH:56]([CH2:72][C:73]([N:75]2[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]2)=[O:74])[C:57]([NH:59][C@H:60]([C:67]([NH:69][C@@H:86]([CH2:95][CH:96]([CH3:98])[CH3:97])[CH:87]([OH:94])[C:88]([O:90][CH:91]([CH3:92])[CH3:93])=[O:89])=[O:68])[CH2:61][C:62]2[N:66]=[CH:65][NH:64][CH:63]=2)=[O:58])[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[CH:47][CH:46]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 13913909isopropyl (2RS,3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochlorideHCID 178511797HCID 178511797, compoundHCID 178514638HCID 178514638, compound

Product 1

HCID 178445967HCID 178445967, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 240 mg of N-[2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidine hydrazide in 3 ml of dry N,N-dimethylformamide were added successively 0.32 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.08 ml of isoamyl nitrite at -20° C. with stirring. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C. and neutralized with 0.23 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 120 mg of isopropyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.07 ml of triethylamine in 2 ml of dry N,N-dimethylformamide under ice-cooling with stirring, and the mixture was stirred for 16 hours. The reaction mixture was evaporated under reduced pressure. 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 separated by silica gel flash column chromatography (eluent: chloroform/methanol=20/1 by volume), and fraction containing desired product which has Rf1 value of 0.63 was combined and purified to obtain 18 mg of isopropyl (2RS, 3S)-3-{N-[ 2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 16 hours
  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 separated by silica gel flash column chromatography (eluent: chloroform/methanol=20/1 by volume), and fraction
  10. additioncontaining desired product which
  11. custompurified

Sources & evidence

ORD record
ord-3b64d62aaf1f42ebaac17f990ec203be
Source dataset
uspto-grants-1987_04
Patent number
US04656269

Reaction notes

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