1,2-Dichloroethane → N'-((2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoyl)-4-cyanobenzohydrazide

HRID 238578

Reaktionsgleichung

Reaktionsgleichung von HRID 238578
[CH2:1]([O:8][C@H:9]([C:25]([F:28])([F:27])[F:26])[C@@H:10]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]([Cl:23])[C:16]=1[CH3:24])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29]([C:31]1[CH:40]=[CH:39][C:34]([C:35]([NH:37][NH2:38])=[O:36])=[CH:33][CH:32]=1)#[N:30].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C1COCC1>[CH2:1]([O:8][C@H:9]([C:25]([F:26])([F:28])[F:27])[C@@H:10]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]([Cl:23])[C:16]=1[CH3:24])[C:11]([NH:38][NH:37][C:35](=[O:36])[C:34]1[CH:33]=[CH:32][C:31]([C:29]#[N:30])=[CH:40][CH:39]=1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 4567324-CyanobenzohydrazideHCID 66624928(2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoic acid

Produkt 1

HCID 66625108N'-((2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoyl)-4-cyanobenzohydrazideAusbeute 47,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

To a solution of (2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoic acid (280 mg) in THF (15 mL) were added 4-cyanobenzohydrazide (130 mg, 0.81 mmol), HOBt (109 mg, 0.81 mmol), EDC (232 mg, 1.21 mmol) and Et3N (0.25 mL, 1.79 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 (200 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 N′-((2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoyl)-4-cyanobenzohydrazide (180 mg, 10%). 1H NMR (400 MHz, CDCl3, δ in ppm) 9.26 (b, 1H), 8.88 (b, 1H), 7.92 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.36˜7.39 (m, 5H), 7.28 (d, J=8.7 Hz, 1H), 6.44 (d, J=8.7 Hz, 1H), 5.22 (d, J=6.6 Hz, 1H), 4.93 (d, J=11.1 Hz, 1H), 4.80 (d, J=11.1 Hz, 1H), 4.66 (m, 1H), 4.33 (d, J=6.6 Hz, 1H), 2.27 (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 (200 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-8caa8c731cee452fa4a49c93738c5f85
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642632B2

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