1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide

HRID 1455603Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1455603
Cl.[NH2:2][C@@:3]([CH3:9])([CH2:6][CH2:7][CH3:8])[CH2:4][OH:5].[F:10][C:11]([F:33])([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:12][C@H:13]([NH:17][C:18]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:19])[C:14](O)=[O:15].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[F:33][C:11]([F:10])([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:12][C@H:13]([NH:17][C:18]([N:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)=[O:19])[C:14](=[O:15])[NH:2][C@@:3]([CH2:4][OH:5])([CH3:9])[CH2:6][CH2:7][CH3:8]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57535341(S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acidHCID 86607351(S)-2-amino-2-methyl-pentan-1-ol hydrochloride

Produkt 1

HCID 86607350morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amideAusbeute 75,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of (S)-2-amino-2-methyl-pentan-1-ol hydrochloride (104.4 mg, 0.67 mmol), (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid (231 mg, 0.67 mmol), EDCI (154 mg, 0.8 mmol), HOBT (108 mg, 0.8 mmol) and Diisopropyl ethylamine (0.23 mL) in DMF (2 mL) is stirred at room temperature overnight. The reaction mixture is diluted with ethyl acetate, washed with cold 1N HCl, saturated NaHCO3 and then saturated NaCl solution. The organic phase is dried over MgSO4 and solvent evaporated under reduced pressure to give the crude product. Purification by Silica gel column chromatography, eluting with ethyl acetate and heptane mixture gives morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide (223 mg, 75%).

Aufarbeitung

  1. washwashed with cold 1N HCl, saturated NaHCO3
  2. dry with materialThe organic phase is dried over MgSO4 and solvent
  3. customevaporated under reduced pressure
  4. customto give the crude product
  5. customPurification by Silica gel column chromatography
  6. washeluting with ethyl acetate and heptane mixture

Quellen und Nachweise

ORD-Eintrag
ord-b0cdd4d63746428d83aef298ac799755
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07482448B2

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