Hydrochloric Acid → HCID 178465090, compound

HRID 542377Notes

Reaction equation

HRID 542377 reaction equation
C1(CC(CC(=O)NCC)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:42]1([CH2:52][CH:53]([CH2:69][C:70](=[O:74])[NH:71][CH2:72][CH3:73])[C:54]([NH:56][C@H:57]([C:64]([N:66]=[N+]=[N-])=[O:65])[CH2:58][C:59]2[N:63]=[CH:62][NH:61][CH:60]=2)=[O:55])[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=[CH:44][CH:43]=1.[N-]=[N+]=[N-].Cl.N[C@@H:80]([CH2:87][CH:88]([CH3:90])[CH3:89])[CH:81]([OH:86])[C:82]([O:84][CH3:85])=[O:83]>CN(C)C=O.C(N(CC)CC)C>[C:42]1([CH2:52][CH:53]([CH2:69][C:70](=[O:74])[NH:71][CH2:72][CH3:73])[C:54]([NH:56][C@H:57]([C:64]([NH:66][C@@H:80]([CH2:87][CH:88]([CH3:90])[CH3:89])[CH:81]([OH:86])[C:82]([O:84][CH3:85])=[O:83])=[O:65])[CH2:58][C:59]2[N:63]=[CH:62][NH:61][CH:60]=2)=[O:55])[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=[CH:44][CH:43]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 13746619methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochlorideHCID 178465091HCID 178465091, compoundHCID 178465092HCID 178465092, compound

Product 1

HCID 178465090HCID 178465090, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 207 mg of N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)propionyl]-L-histidine hydrazide in 3 ml of dry N,N-dimethylformamide were added successively 0.30 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.076 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 0.22 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 100 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.66 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 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=15/1, Rf1 =0.43) to obtain 77 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)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. washthe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by silica gel flash column chromatography (eluent chloroform/methanol=15/1, Rf1 =0.43)

Sources & evidence

ORD record
ord-cd47c4f435fb45c098a9182aa7e0bf07
Source dataset
uspto-grants-1987_04
Patent number
US04656269

Reaction notes

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