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

HRID 563330

Reaktionsgleichung

Reaktionsgleichung von HRID 563330
[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].[N+:19]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)([O-:21])=[O:20].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:29][NH:28][C:26](=[O:27])[C:25]2[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:31][CH:30]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 3693744Benzoic acid, 4-nitro-, hydrazideHCID 57908625(2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid2×

Produkt 1

HCID 67006072N'-((2R,3R)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-nitrobenzohydrazideAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a pre-cooled (−45° C.) solution of (2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (intermediate 3a) (18.54 g, 69.0 mmol) and 4-nitrobenzohydrazide (12.5 g, 69.0 mmol) in anhydrous THF (400 mL) was added 1-Hydroxybenzotriazole monohydrate (10.57 g, 69.0 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide-HCl (26.46 g, 138.0 mmol) at −45° C. followed by triethylamine (19.2 mL, 138.0 mmol). The reaction mixture warmed to room temperature and stirred for 66 h, then quenched with 5% aq. citric acid (350 mL). The solution was extracted with EtOAc (300 mL). The organic extract was washed with 5% aq. citric acid (2×300 mL), sat. aq. NaHCO3 (3×300 mL), H2O (2×300 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a yellow solid (26.4 g, 89%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 8.37 (dm, J=9.0 Hz, 2H), 8.18 (dm, J=9.0 Hz, 2H), 7.54 (d, J=8.6 Hz, 1H), 6.75 (d, J=8.4 Hz, 1H), 5.59 (d, J=7.2 Hz, 1H), 4.29 (pentet, J=5.3 Hz, 1H), 4.17 (dd, J=5.1, 7.2 Hz, 1H), 2.36 (s, 3H), 1.40 (d, J=6.5 Hz, 3H).

Aufarbeitung

  1. customquenched with 5% aq. citric acid (350 mL)
  2. extractionThe solution was extracted with EtOAc (300 mL)
  3. extractionThe organic extract
  4. washwas washed with 5% aq. citric acid (2×300 mL), sat. aq. NaHCO3 (3×300 mL), H2O (2×300 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-9e7a8b8dcdbe4694872cda8aa3c643a8
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067448B2

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