Triethylamine → N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(trifluoromethyl)benzohydrazide

HRID 563328

Reaktionsgleichung

Reaktionsgleichung von HRID 563328
[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[F:19][C:20]([F:32])([F:31])[C:21]1[CH:30]=[CH:29][C:24]([C:25]([NH:27][NH2:28])=[O:26])=[CH:23][CH:22]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([NH:28][NH:27][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:32])[F:31])=[CH:30][CH:29]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 5206624-(Trifluoromethyl)benzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine2×

Produkt 1

HCID 67005862N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(trifluoromethyl)benzohydrazide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a pre-cooled (−45° C.) solution of (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (intermediate 1a) (1.97 g, 7.35 mmol) and 4-(trifluoromethyl)benzohydrazide (1.50 g, 7.35 mmol) in anhydrous THF (80 mL) was added 1-Hydroxybenzotriazole monohydrate (1.13 g, 7.35 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide-HCl (2.82 g, 14.7 mmol) at −45° C. followed by triethylamine (2.0 mL, 14.7 mmol). The reaction mixture warmed to room temperature and stirred for 23 h, then quenched with 5% aq. citric acid (300 mL). The solution was extracted with EtOAc (300 mL). The organic extract was washed with 5% aq. citric acid (2×150 mL), sat. aq. NaHCO3 (3×150 mL), H2O (2×150 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a off white solid (3.09 g, 92%): 1H NMR (400 MHz, d6-DMSO, δ in ppm) 10.71 (s, 1H), 10.31 (s, 1H), 8.05 (d, J=8.2 Hz, 2H), 7.89 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.6 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.67 (d, J=7.6 Hz, 1H), 5.31 (d, J=5.7 Hz, 1H), 4.14 (sextet, J=6.1 Hz, 1H), 3.94 (dd, J=5.7, 7.2 Hz, 1H), 2.30 (s, 3H), 1.28 (d, J=6.3 Hz, 3H).

Aufarbeitung

  1. customquenched with 5% aq. citric acid (300 mL)
  2. extractionThe solution was extracted with EtOAc (300 mL)
  3. extractionThe organic extract
  4. washwas washed with 5% aq. citric acid (2×150 mL), sat. aq. NaHCO3 (3×150 mL), H2O (2×150 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-6b1777090d4040448c4c81e8c8bcc5b5
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067448B2

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