Hydrochloric Acid → (2R, 4S, 5S)-5-{N-[2(R)-Benzyl-3-(morpholinocarbonyl)propionyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2,N-dimethylhexanamide

HRID 1768834Notes

Reaction equation

HRID 1768834 reaction equation
C(O[C:6]([NH:8][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C@@H:20]([OH:28])[CH2:21][C@@H:22]([CH3:27])[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:7])(C)(C)C.Cl.[CH2:37]([C@H:44]([CH2:48][C:49]([N:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1)=[O:50])C(O)=O)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C>O1CCOCC1.CO>[CH2:37]([C@H:44]([CH2:48][C:49]([N:51]1[CH2:52][CH2:53][O:54][CH2:55][CH2:56]1)=[O:50])[C:6]([NH:8][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:29][CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)[C@@H:20]([OH:28])[CH2:21][C@@H:22]([CH3:27])[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:7])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 142130822(R)-benzyl-3-(morpholinocarbonyl)propionic acidHCID 15045762(2R, 4S, 5S)-5-[N-(t-Butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2, N-dimethylhexanamide

Product 1

HCID 15045748(2R, 4S, 5S)-5-{N-[2(R)-Benzyl-3-(morpholinocarbonyl)propionyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2,N-dimethylhexanamideYield 34.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 110 mg (0.215 mmole) of (2R, 4S, 5S)-5-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2,N-dimethylhexanamide [prepared as described in step (a) above], 2 ml of methanol and 2 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure. The residue was mixed with benzene and the solvent was stripped from the mixture by distillation under reduced pressure. After this operation had been repeated three times, the final residue was dried in vacuo for 8 hours. The dried material was then suspended in 8 ml of anhydrous tetrahydrofuran, and 59.6 mg (0.215 mmole) of 2(R)-benzyl-3-(morpholinocarbonyl)propionic acid were added to the suspension. 0.042 ml (0.258 mmole) of 95% diethyl cyanophosphonate and 0.12 ml (0.86 mmole) of triethylamine were then added to the mixture, and the resulting mixture was stirred for 18 hours. At the end of this time, the reaction mixture was concentrated by distillation under reduced pressure, and the residue was purified by preparative thin layer chromatography on silica gel (using a 10:1 by volume mixture of methylene chloride and methanol as the developing solvent), to afford 50 mg of the title compound as a white powder.

Workup

  1. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  2. additionThe residue was mixed with benzene
  3. distillationthe solvent was stripped from the mixture by distillation under reduced pressure
  4. dry with materialthe final residue was dried in vacuo for 8 hours
  5. stirringthe resulting mixture was stirred for 18 hours
  6. concentrationAt the end of this time, the reaction mixture was concentrated by distillation under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography on silica gel (
  8. additionby volume mixture of methylene chloride and methanol as the developing solvent),

Sources & evidence

ORD record
ord-795208f94bb44a038e281f7d5b2f8e07
Source dataset
uspto-grants-1995_01
Patent number
US05378689

Reaction notes

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