Hydrochloric Acid → 5-{N-[2(R)-Benzyl-4-oxopentanoyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide

HRID 2380102Notes

Reaction equation

HRID 2380102 reaction equation
C(OC([NH:8][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)[C@@H:20]([OH:31])[CH2:21][C@@H:22]([C:27]([OH:30])([CH3:29])[CH3:28])[C:23]([NH:25][CH3:26])=[O:24])=[O:17])[CH2:10][C:11]1[N:12]=[CH:13][S:14][CH:15]=1)=O)(C)(C)C.Cl.[CH2:40]([C@H:47]([CH2:51][C:52](=[O:54])[CH3:53])[C:48]([OH:50])=O)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.P(C#N)(OCC)(OCC)=O.C(N(CC)CC)C>O1CCOCC1>[CH2:40]([C@H:47]([CH2:51][C:52](=[O:54])[CH3:53])[C:48]([NH:8][C@H:9]([C:16]([NH:18][CH:19]([CH2:32][CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1)[CH:20]([OH:31])[CH2:21][CH:22]([C:27]([OH:30])([CH3:28])[CH3:29])[C:23]([NH:25][CH3:26])=[O:24])=[O:17])[CH2:10][C:11]1[N:12]=[CH:13][S:14][CH:15]=1)=[O:50])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 149890802(R)-benzyl-4-oxopentanoic acidHCID 14989089(2S, 4S, 5S)-5-[N-(t-Butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide

Product 1

HCID 545589915-{N-[2(R)-Benzyl-4-oxopentanoyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamideYield 74%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture or 192 mg (0.35 mmoles) of (2S, 4S, 5S)-5-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide [prepared as described in Example 9(a)] in 2 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature under an atmosphere of nitrogen for 30 minutes. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure. Diethyl ether was added to the residue, and the solvent was again removed by distillation under reduced pressure. The same operation was repeated, in total, three times. The resulting residue was dried by evaporation under reduced pressure for 8 hours, and was then suspended in 5 ml of anhydrous tetrahydrofuran. 86 mg (0.42 mmoles) of 2(R)-benzyl-4-oxopentanoic acid (prepared as described in Preparation 20) were then added to the suspension, after which 0.06 ml (0.40 mmoles) of diethyl cyanophosphate and 0.16 ml (1.15 mmoles) of triethylamine were added to the mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 3 hours, after which the solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (using an 8:1 by volume mixture of methylene chloride and methanol as the developing solvent), to give 164 mg (yield 74%) of the title compound as an amorphous substance.

Workup

  1. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  2. additionDiethyl ether was added to the residue
  3. customthe solvent was again removed by distillation under reduced pressure
  4. customThe resulting residue was dried by evaporation under reduced pressure for 8 hours
  5. temperaturecooling and under an atmosphere of nitrogen
  6. customafter which the solvent was removed by distillation under reduced pressure
  7. customthe resulting residue was purified by silica gel thin layer chromatography (
  8. additionby volume mixture of methylene chloride and methanol as the developing solvent),

Sources & evidence

ORD record
ord-5b6339333bc04d538659952cd0932cdb
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

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