1,2-Dichloroethane → (R)-N'-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazide

HRID 238570

Reaktionsgleichung

Reaktionsgleichung von HRID 238570
[Cl:1][C:2]1[C:3]([CH3:19])=[C:4]([NH:10][C@H:11]([C:15]([OH:18])([CH3:17])[CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[C:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)#[N:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:19])=[C:4]([NH:10][C@H:11]([C:15]([OH:18])([CH3:17])[CH3:16])[C:12]([NH:29][NH:28][C:26](=[O:27])[C:25]2[CH:24]=[CH:23][C:22]([C:20]#[N:21])=[CH:31][CH:30]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 4567324-CyanobenzohydrazideHCID 66625199(R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoic acid

Produkt 1

HCID 66625521(R)-N'-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazideAusbeute 65,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

To a solution of (R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoic acid (3.5 g, 12.4 mmol) in THF (80 mL) were added 4-cyanobenzhydrazide (2.3 g, 14.3 mmol), HOBt (1.70 g, 12.6 mmol), EDC (3.56 g, 18.6 mmol) and Et3N (2.8 mL, 20.1 mmol) at −20° C. sequentially. After addition, the mixture was stirred at −20° C. for 30 min., then room temperature overnight. The reaction was quenched by adding ice-water. After removal of the THF, the residue was extracted with EtOAc (300 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. The filtrate was concentrated and purified by flash chromatography to give the title compound (R)—N′-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazide (3.47 g, 65%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 9.72 (b, 2H), 8.08 (d, J=8.4 Hz, 2H), 7.92 (d, J=8.4 Hz, 2H), 7.52 (d, J=8.6 Hz, 1H), 6.72 (d, J=8.6 Hz, 1H), 5.55 (d, J=7.2 Hz, 1H), 4.08 (d, J=7.2 Hz, 1H), 2.35 (s, 3H), 1.47 (s, 3H), 1.42 (s, 3H).

Aufarbeitung

  1. additionAfter addition
  2. customroom temperature overnight
  3. customThe reaction was quenched
  4. additionby adding ice-water
  5. customAfter removal of the THF
  6. extractionthe residue was extracted with EtOAc (300 mL)
  7. washThe EtOAc extracts were washed with water, brine
  8. dry with materialdried over Na2SO4
  9. concentrationThe filtrate was concentrated
  10. custompurified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-86367227076242a39b5bbc5bd89f5b50
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642632B2

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