4-Cyanobenzohydrazide → (R)-4-cyano-N'-(2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoyl)benzohydrazide

HRID 238564

Reaktionsgleichung

Reaktionsgleichung von HRID 238564
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:14]([OH:17])([CH3:16])[CH3:15])[C:11](O)=[O:12])=[C:5]([CH3:18])[C:4]=1[C:19]([F:22])([F:21])[F:20])#[N:2].[C:23]([C:25]1[CH:34]=[CH:33][C:28]([C:29]([NH:31][NH2:32])=[O:30])=[CH:27][CH:26]=1)#[N:24].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1.C(OCC)(=O)C>[C:23]([C:25]1[CH:26]=[CH:27][C:28]([C:29]([NH:31][NH:32][C:11](=[O:12])[C@H:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:19]([F:22])([F:21])[F:20])[C:5]=2[CH3:18])[C:14]([OH:17])([CH3:16])[CH3:15])=[O:30])=[CH:33][CH:34]=1)#[N:24]

Komponenten

7

Edukt 4

HCID 4567324-CyanobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66624722(R)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoic acidHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 66625266(R)-4-cyano-N'-(2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoyl)benzohydrazideAusbeute 108,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

(R)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoic acid (500 mg, 1.58 mmol) and 4-cyanobenzohydrazide (301 mg, 1.87 mmol) were mixed together in THF (20 mL) and cooled to −15° C. under N2 atmosphere. To the pre-cooled reaction mixture were added hydroxybenzotriazole (HOBT) (230 mg, 1.70 mmol), TEA (0.36 mL, 2.55 mmol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (489 mg, 2.55 mmol). The reaction mixture was allowed to stir at −20° C. for 20 min and then at room temperature overnight. After the reaction was complete, ethyl acetate (50 mL) was added and the solution was washed with 5% citric acid (2×40 mL), 5% NaHCO3 (2×40 mL) followed by water (40 mL) and then dried (Na2SO4) to provide the crude product as a yellow solid (790 mg, 99%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.92 (br s, 1H), 9.49 (br s, 1H), 7.99 (d, J=9 Hz, 2H), 7.81 (d, J=9 Hz, 2H), 7.42 (d, J=9 Hz, 1H), 6.61 (d, J=9 Hz, 1H), 6.53 (dd, J=12 and 18 Hz, 1H), 5.99 (d, J=9 Hz, 1H), 5.73 (dd, J=2 and 12 Hz, 2H), 5.64 (dd, J=2 and 18 Hz), 4.29-4.22 (m, 1H), 4.01-3.99 (m, 1H) and 1.20 (d, J=7 Hz, 3H).

Aufarbeitung

  1. customTo the pre-cooled reaction mixture
  2. customat room temperature
  3. customovernight
  4. washthe solution was washed with 5% citric acid (2×40 mL), 5% NaHCO3 (2×40 mL)
  5. dry with materialdried (Na2SO4)

Quellen und Nachweise

ORD-Eintrag
ord-02988b041b1345d99f3abaac86714458
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642632B2

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