1-Naphthalenemethanamine, alpha-methyl-, (alphaS)- → 2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[(1S)-1-(1-naphthyl)ethyl]propionamide

HRID 660930

Reaktionsgleichung

Reaktionsgleichung von HRID 660930
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]3[CH2:15][CH2:14]3)[C:11](=[O:16])[N:10]([CH:17]([CH3:21])[C:18]([OH:20])=O)[N:9]=2)=[CH:4][CH:3]=1.[C:22]1([C@@H:32]([NH2:34])[CH3:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH:13]3[CH2:14][CH2:15]3)[C:11](=[O:16])[N:10]([CH:17]([CH3:21])[C:18]([NH:34][C@H:32]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)[CH3:33])=[O:20])[N:9]=2)=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 663251-Naphthalenemethanamine, alpha-methyl-, (alphaS)-HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58011743Rac-2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1h-1,2,4-triazol-1-yl]propionic acid

Produkt 1

HCID 580116372-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[(1S)-1-(1-naphthyl)ethyl]propionamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

100.0 mg (0.325 mmol) of 2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-propionic acid from Example 105A are placed in 2 ml of DMF and treated with 61.2 mg (0.357 mmol) of (1S)-1-(1-naphthyl)ethanamine, 52.7 mg (0.390 mmol) of HOBt and 81.0 mg (0.422 mmol) of EDC hydrochloride. The mixture is stirred overnight at room temperature, then partitioned between dichloromethane and water, and the organic phase is separated, dried over sodium sulphate and concentrated. The residue is purified by flash chromato-graphy on silica gel (eluent: first dichloromethane, then dichloromethane/methanol 100:1) and then further separated by preparative HPLC on chiral phase [Method 15]. 52 mg (35% of theory) of the diastereomerically pure target compound are thus obtained (see also Example 187).

Aufarbeitung

  1. custompartitioned between dichloromethane and water
  2. customthe organic phase is separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe residue is purified by flash chromato-graphy on silica gel (eluent
  6. customfirst dichloromethane, then dichloromethane/methanol 100:1) and then further separated by preparative HPLC on chiral phase [Method 15]
  7. custom52 mg (35% of theory) of the diastereomerically pure target compound are thus obtained (

Quellen und Nachweise

ORD-Eintrag
ord-91e6e36ead9849e19f77cf636786ec83
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084481B2

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