Hydrochloric Acid → (2S, 4S, 5S)-5-{N-[2(R)-Benzyl-3-(morpholinocarbonyl)propionyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-butylhexanamide

HRID 2380115노트

반응식

HRID 2380115 반응식
C(C([NH:7][C@H:8]([C:15]([NH:17][C@@H:18]([CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1)[C@@H:19]([OH:33])[CH2:20][C@@H:21]([C:29]([OH:32])([CH3:31])[CH3:30])[C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:23])=[O:16])[CH2:9][C:10]1[N:11]=[CH:12][S:13][CH:14]=1)=O)(C)(C)C.Cl.[CH2:42]([C@H:49]([CH2:53][C:54]([N:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1)=[O:55])[C:50]([OH:52])=O)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.P(C#N)(OCC)(OCC)=O.C(N(CC)CC)C>O1CCOCC1>[CH2:42]([C@H:49]([CH2:53][C:54]([N:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1)=[O:55])[C:50]([NH:7][C@H:8]([C:15]([NH:17][C@@H:18]([CH2:34][CH:35]1[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]1)[C@@H:19]([OH:33])[CH2:20][C@@H:21]([C:29]([OH:32])([CH3:30])[CH3:31])[C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:23])=[O:16])[CH2:9][C:10]1[N:11]=[CH:12][S:13][CH:14]=1)=[O:52])[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 142130822(R)-benzyl-3-(morpholinocarbonyl)propionic acidHCID 86748262(2S, 4S, 5S)-5-[N-(t-butylcarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-butylhexanamide

생성물 1

HCID 70055695(2S, 4S, 5S)-5-{N-[2(R)-Benzyl-3-(morpholinocarbonyl)propionyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-butylhexanamide수율 90.5%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A mixture of 200.7 mg (0.336 mmole) of (2S, 4S, 5S)-5-[N-(t-butylcarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-butylhexanamide in 6 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes under an atmosphere of nitrogen. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and then benzene was added to the residue. The solvent was removed by distillation under reduced pressure from the resulting solution. The same operation was repeated, in total, three times, and the residue was then dried by evaporation under reduced pressure for 8 hours. The dried material was then suspended in 10 ml of anhydrous tetrahydrofuran, and 98.2 mg (0.354 mmole) of 2(R)-benzyl-3-(morpholinocarbonyl)propionic acid were added to the suspension. 0.06 ml (0.396 mmole) of 95% diethyl cyanophosphate and 0.2 ml (0.143 mmole) of triethylamine were then added to the resulting mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 8 hours, after which the solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography (using a 20:1 by volume mixture of methylene chloride and methanol as eluent), followed by recrystallization from a mixture of ethyl acetate and diisopropyl ether, to give 229.8 mg of the title compound as white crystals, melting at 92°-95° C.

후처리

  1. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  2. additionbenzene was added to the residue
  3. customThe solvent was removed by distillation under reduced pressure from the resulting solution
  4. customthe residue was then dried by evaporation under reduced pressure for 8 hours
  5. temperaturecooling and under an atmosphere of nitrogen
  6. stirringThe mixture was then stirred for 8 hours
  7. customafter which the solvent was removed by distillation under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (
  9. additionby volume mixture of methylene chloride and methanol as eluent),
  10. customfollowed by recrystallization from a mixture of ethyl acetate and diisopropyl ether

출처 및 근거

ORD 기록
ord-86a555b98b4a4dbea0700e04f0ada664
출처 데이터셋
uspto-grants-1994_11
특허 번호
US05364844

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