Lithium hydroxide, monohydrate → N,beta,beta-trimethyl-L-phenylalanyl-N1,3-dimethyl-N1-{(1S)-2-methyl-1-[(Z)-(3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl]propyl}-L-valinamide

HRID 1865739Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1865739
C(OP([CH:9]1[C:13](=[O:14])[NH:12][C:11](=[O:15])[N:10]1[CH3:16])(=O)OCC)C.O.[OH-].[Li+].[CH:20]([CH:22]([N:26]([CH3:49])[C:27]([CH:29]([NH:34][C:35](=[O:48])[CH:36]([NH:46][CH3:47])[C:37]([CH3:45])([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH3:38])[C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:23]([CH3:25])[CH3:24])=O>C(O)C.O>[CH3:47][NH:46][C@H:36]([C:35]([NH:34][C@H:29]([C:27]([N:26]([CH3:49])[C@H:22](/[CH:20]=[C:9]1\[N:10]([CH3:16])[C:11](=[O:15])[NH:12][C:13]\1=[O:14])[CH:23]([CH3:24])[CH3:25])=[O:28])[C:30]([CH3:31])([CH3:32])[CH3:33])=[O:48])[C:37]([CH3:38])([CH3:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Komponenten

6

Edukt 3

HCID 168937Lithium hydroxide, monohydrateHCID 13937024Diethyl (3-methyl-2,5-dioxoimidazolidin-4-yl)phosphonateHCID 72370856N-{1-[(1-Formyl-2-methyl-propyl)-methyl-carbamoyl]-2,2-dimethyl-propyl}-3-methyl-2-methylamino-3-phenyl-butyramide

Produkt 1

HCID 44393187N,beta,beta-trimethyl-L-phenylalanyl-N1,3-dimethyl-N1-{(1S)-2-methyl-1-[(Z)-(3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl]propyl}-L-valinamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittel2×HCID 962WaterLösungsmittel

Versuchsvorschrift

The yield, (3-methyl-2,5-dioxo-imidazolidin-4-yl)-phosphonic acid diethyl ester (0.915 g, 3.0 mmol) in ethanol (9 mL) is added to lithium hydroxide monohydrate (139 mg, 2.1 mmol) in 0.9 ml water to give a yellow solution. It is then added to N-{1-[(1-formyl-2-methyl-propyl)-methyl-carbamoyl]-2,2-dimethyl-propyl}-3-methyl-2-methylamino-3-phenyl-butyramide (˜1 mmol, from Reference Example 12) in 3 mL ethanol. The reaction mixture is stirred at room temperature for 60 hours. Solvent is evaporated. The residue is diluted with dichloromethane/water. The aqueous layer is extracted twice with dichloromethane. The combined organic extracts are washed with brine, dried oversodium sulfate, filtered and concentrated in vacuo. The residue is chromatographed by reverse phase HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a white solid, N,beta,beta-trimethyl-L-phenylalanyl-N1,3-dimethyl-N1-{(1S)-2-methyl-1-[(Z)-(3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl]propyl}-L-valinamide: 25 mg (4%) MS (ES+): (M+H)=514.3

Aufarbeitung

  1. customto give a yellow solution
  2. customSolvent is evaporated
  3. additionThe residue is diluted with dichloromethane/water
  4. extractionThe aqueous layer is extracted twice with dichloromethane
  5. washThe combined organic extracts are washed with brine
  6. dry with materialdried oversodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is chromatographed by reverse phase HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

Quellen und Nachweise

ORD-Eintrag
ord-c12bf9d16c6e4bca8a8ae12022ba53df
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07626023B2

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