Hydrochloric Acid → N-{4(S)-[N-Benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(2-thienyl)-DL-alanyl]amino-3(S)-hydroxy-6-methylheptanoyl}-L-isoleucinol

HRID 255625Notes

Reaction equation

HRID 255625 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24]([NH:26][CH:27]([C:34]([NH:36]N)=[O:35])[CH2:28][C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)=[O:25])[CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.CN1CC[O:43]CC1.Cl.N[C@@H:48]([CH3:65])[C@@:49](O)([CH3:63])[C@@H:50]([CH2:61][OH:62])[NH:51][C:52](=[O:60])[CH2:53][CH2:54][CH2:55][CH2:56][CH:57]([CH3:59])[CH3:58]>CN(C)C=O.O1CCOCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24]([NH:26][CH:27]([C:34]([NH:36][C@@H:55]([CH2:56][CH:57]([CH3:59])[CH3:58])[C@@H:54]([OH:43])[CH2:53][C:52]([NH:51][C@H:50]([CH2:61][OH:62])[C@H:49]([CH2:48][CH3:65])[CH3:63])=[O:60])=[O:35])[CH2:28][C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)=[O:25])[CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 13961464N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(2-thienyl)-DL-alanine hydrazideHCID 867418294(S)-amino-3(S)-hydroxy-6-methylheptanoyl-L-isoleucinol hydrochloride

Product 1

HCID 53648204N-{4(S)-[N-Benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(2-thienyl)-DL-alanyl]amino-3(S)-hydroxy-6-methylheptanoyl}-L-isoleucinolYield 13.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-60 °C

Procedure

517 mg (1 mmole) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(2-thienyl)-DL-alanine hydrazide were dissolved in 10 ml of dimethylformamide, and the solution was cooled down to -60° C. 0.85 ml (3.4 mmole) of 4N hydrogen chloride in dioxane was then added. The temperature of this mixture was elevated to -20° C., and then 0.16 ml (1.19 mmole) of isoamyl nitrile was added and the mixture was stirred for 10 minutes. The reaction product was again cooled down to -60° C., and 0.42 ml (3.82 mmole) of N-methylmorpholine was added for neutralization. Subsequently, 370 mg (1.2 mmole) of 4(S)-amino-3(S)-hydroxy-6-methylheptanoyl-L-isoleucinol hydrochloride were added, and the mixture was stirred for 30 minutes. The reaction product was stirred overnight at 0° C., condensed by evaporation under reduced pressure and purified by thin layer chromatography, using as developing solvent a 99:1 by volume mixture of chloroform and methanol, to yield 100 mg (13.2%) of the title compound melting at 160°-162° C., [α]23 -61.7° (C=0.3, dimethylformamide).

Workup

  1. customwas elevated to -20° C.
  2. additionwas added for neutralization
  3. stirringthe mixture was stirred for 30 minutes
  4. stirringThe reaction product was stirred overnight at 0° C.
  5. customcondensed
  6. customby evaporation under reduced pressure
  7. custompurified by thin layer chromatography
  8. additionby volume mixture of chloroform and methanol

Sources & evidence

ORD record
ord-f86c276c01a746228ccb324b661040d9
Source dataset
uspto-grants-1987_10
Patent number
US04698329

Reaction notes

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