Trifluoroacetic acid → (2R,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid (2,2-dimethylpropyl)amide hemifumarate

HRID 1694966Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1694966
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][C@@H:15]([CH2:29][N:30]1[CH2:35][C:34](=[O:36])[N:33]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[CH3:43])[CH2:32][C:31]1([CH3:45])[CH3:44])[C@@H:16]([OH:28])[CH2:17][C@H:18]([C:20](=[O:27])[NH:21][CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])(C)(C)C.[C:47]([OH:54])(=[O:53])/[CH:48]=[CH:49]/[C:50]([OH:52])=[O:51].[CH3:55][C:56]([CH3:86])([CH3:85])[CH2:57][NH:58][C:59](=[O:84])[C@H:60]([CH3:83])[CH2:61][C@H:62]([OH:82])[C@@H:63]([NH2:81])[CH2:64][N:65]1[CH2:70][C:69](=[O:71])[N:68]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=2[CH3:78])[CH2:67][C:66]1([CH3:80])[CH3:79]>C(Cl)Cl.CO>[C:47]([OH:54])(=[O:53])/[CH:48]=[CH:49]/[C:50]([OH:52])=[O:51].[CH3:25][C:23]([CH3:24])([CH3:26])[CH2:22][NH:21][C:20](=[O:27])[C@H:18]([CH3:19])[CH2:17][C@H:16]([OH:28])[C@@H:15]([NH2:14])[CH2:29][N:30]1[CH2:35][C:34](=[O:36])[N:33]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[CH3:43])[CH2:32][C:31]1([CH3:44])[CH3:45].[NH2:81][C@@H:63]([CH2:64][N:65]1[CH2:70][C:69](=[O:71])[N:68]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=2[CH3:78])[CH2:67][C:66]1([CH3:79])[CH3:80])[C@@H:62]([OH:82])[CH2:61][C@@H:60]([CH3:83])[C:59]([NH:58][CH2:57][C:56]([CH3:86])([CH3:85])[CH3:55])=[O:84]

Komponenten

7

Edukt 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 66645452{(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl esterHCID 66645647(2r,4s,5s)-5-Amino-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid (2,2-dimethylpropyl)amide

Produkt 1

HCID 131729639(2R,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid (2,2-dimethylpropyl)amide hemifumarateAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

0.71 ml of trifluoroacetic acid (9.16 mmol) was added to a solution of 167 mg of {(1S,2S,4R)-4-(2,2-dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl ester obtained in Example (85c) (0.31 mmol) in methylene chloride (1.4 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. After concentration under reduced pressure, a saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=100/10/1). 18 mg of fumaric acid (0.15 mmol) was added to a solution of 135 mg of (2R,4S,5S)-5-amino-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid (2,2-dimethylpropyl)amide obtained above (0.3 mmol) in methanol (3 ml), and the mixture was stirred at room temperature for five minutes. The reaction mixture was concentrated under reduced pressure, and methylene chloride (0.5 ml) was added to the residue. Diisopropyl ether (5 ml) was further added and the solid was collected by filtration to obtain 145 mg of the title compound (yield: 99%).

Aufarbeitung

  1. concentrationAfter concentration under reduced pressure
  2. additiona saturated sodium bicarbonate aqueous solution was added to the reaction mixture
  3. extractionfollowed by extraction with methylene chloride
  4. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=100/10/1)
  8. stirringthe mixture was stirred at room temperature for five minutes
  9. concentrationThe reaction mixture was concentrated under reduced pressure, and methylene chloride (0.5 ml)
  10. additionwas added to the residue
  11. additionDiisopropyl ether (5 ml) was further added
  12. filtrationthe solid was collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-bb456ce5b6e646919458bc29587cdb40
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158790B2

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