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 2380115ノート

反応式

HRID 2380115 の反応式
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

参加物

7

反応物 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

生成物 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-butylhexanamide収率 90.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-86a555b98b4a4dbea0700e04f0ada664
出典データセット
uspto-grants-1994_11
特許番号
US05364844

反応ノート

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