Hydrochloric Acid → HCID 178445968, compound

HRID 542373Notes

Reaction equation

HRID 542373 reaction equation
N[C@H](C(NN)=O)CC1N=CNC=1.Cl.N(OCCC(C)C)=O.[C:22]1([CH2:32][CH:33]([CH2:49][C:50]([N:52]2[CH2:57][CH2:56][O:55][CH2:54][CH2:53]2)=[O:51])[C:34]([NH:36][C@H:37]([C:44]([N:46]=[N+]=[N-])=[O:45])[CH2:38][C:39]2[N:43]=[CH:42][NH:41][CH:40]=2)=[O:35])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.[N-]=[N+]=[N-].Cl.N[C@@H:63]([CH2:72][CH:73]([CH3:75])[CH3:74])[CH:64]([OH:71])[C:65]([O:67][CH:68]([CH3:70])[CH3:69])=[O:66].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(N(CC)CC)C>[C:22]1([CH2:32][CH:33]([CH2:49][C:50]([N:52]2[CH2:57][CH2:56][O:55][CH2:54][CH2:53]2)=[O:51])[C:34]([NH:36][C@H:37]([C:44]([NH:46][C@@H:63]([CH2:72][CH:73]([CH3:75])[CH3:74])[CH:64]([OH:71])[C:65]([O:67][CH:68]([CH3:69])[CH3:70])=[O:66])=[O:45])[CH2:38][C:39]2[N:43]=[CH:42][NH:41][CH:40]=2)=[O:35])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 33558AzideHCID 516892Sodium BicarbonateHCID 13913909isopropyl (2RS,3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochlorideHCID 178514454HCID 178514454, compoundHCID 178514639HCID 178514639, compound

Product 1

HCID 178445968HCID 178445968, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 50 mg of N-[2-(1-naphthylmethyl)-3-morpholinocarbonyl)propionyl]-L-histidine hydrazide in 1 ml of N,N-dimethylformamide were added successively 0.068 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.017 ml of isoamyl nitrite at -20° C. with stirring. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and the reaction mixture was neutralized by adding 0.048 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 25 mg of isopropyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.032 ml of triethylamine in 2 ml of N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours. A 5% aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with a saturated sodium chloride, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol=5/1 by volume Rf2 =0.53 to obtain 4 mg of isopropyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washwashed with a saturated sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by preparative silica gel thin layer chromatography (

Sources & evidence

ORD record
ord-919106abde5649a5b142cc77ff7b05b5
Source dataset
uspto-grants-1987_04
Patent number
US04656269

Reaction notes

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