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

HRID 1768830Notes

Reaction equation

HRID 1768830 reaction equation
C([O:5][C:6]([NH:8][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[C@@H:20]([OH:30])[CH2:21][C@@H:22]([CH:27]([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.[CH2:39]([C@H:46]([CH2:50][C:51]([N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)=[O:52])C(O)=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C>O1CCOCC1>[CH2:39]([C@H:46]([CH2:50][C:51]([N:53]1[CH2:54][CH2:55][O:56][CH2:57][CH2:58]1)=[O:52])[C:6]([NH:8][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[C@@H:20]([OH:30])[CH2:21][C@@H:22]([CH:27]([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:5])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 142130822(R)-benzyl-3-(morpholinocarbonyl)propionic acidHCID 15045729(2S, 4S, 5S)-5-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-isopropyl-N-methylhexanamide

Product 1

HCID 15045730(2S, 4S, 5S)-5-{N-[2(R)-Benzyl-3-(morpholinocarbonyl)propionyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-isopropyl-N-methylhexanamideYield 72%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 300 mg (0.56 mmole) of (2S, 4S, 5S)-5-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-isopropyl-N-methylhexanamide [prepared as described in Example 1(a)] and 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. The solvent was then removed by distillation under reduced pressure. Diethyl ether was added to the residue, and the mixture was concentrated by evaporation under reduced pressure. This operation was repeated three times. After the final residue had been dried under reduced pressure for 8 hours, the dried material was suspended in 10 ml of anhydrous tetrahydrofuran. 170 mg (0.61 mmole) of 2(R)-benzyl-3-(morpholinocarbonyl)propionic acid were then added to the suspension. 0.09 ml (0.59 mmole) of 95% diethyl cyanophosphonate and 0.26 ml (1.86 mmole) of triethylamine were then added to the resulting mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred at room temperature for 8 hours, after which the solvent was removed by distillation under reduced pressure. The resulting 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 281 mg (yield 72%) of the title compound as white crystals, melting at 83°-86° C.

Workup

  1. customThe solvent was then removed by distillation under reduced pressure
  2. additionDiethyl ether was added to the residue
  3. concentrationthe mixture was concentrated by evaporation under reduced pressure
  4. dry with materialAfter the final residue had been dried under reduced pressure for 8 hours
  5. temperaturecooling and under an atmosphere of nitrogen
  6. stirringThe mixture was then stirred at room temperature for 8 hours
  7. customafter which the solvent was removed by distillation under reduced pressure
  8. customThe resulting residue was purified by preparative thin layer chromatography on silica gel (
  9. additionby volume mixture of methylene chloride and methanol as the developing solvent),

Sources & evidence

ORD record
ord-86386319fa2c472daa94a40e80125d64
Source dataset
uspto-grants-1995_01
Patent number
US05378689

Reaction notes

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