Hydrochloric Acid → HCID 178501837, compound

HRID 542376Notes

Reaction equation

HRID 542376 reaction equation
C1(CC(CC(=O)N(C)C)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])[N:71]([CH3:73])[CH3:72])[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])[N:71]([CH3:73])[CH3:72])[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 178484532HCID 178484532, compoundHCID 178484533HCID 178484533, compound

Product 1

HCID 178501837HCID 178501837, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 100 mg of N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)propionyl]-L-histidine hydrazide in 5 ml of dry N,N-dimethylformamide were added successively 0.15 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.04 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 0.11 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 50 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.04 ml of triethylamine in 5 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 dried over anhydrous magnesium sulfate and evaporated reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: a lower layer of chloroform/methanol/water=8/3/1, Rf1 = 0.69) to obtain 20 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)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. dry with materialthe ethyl acetate layer was dried over anhydrous magnesium sulfate
  6. customevaporated reduced pressure
  7. customThe residue was purified by preparative silica gel thin layer chromatography (

Sources & evidence

ORD record
ord-141b5f60296a4c56803ad3576766b5d6
Source dataset
uspto-grants-1987_04
Patent number
US04656269

Reaction notes

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