1,2-Dichloroethane → 7-(3,5-dimethylisoxazol-4-yl)-8-methoxy-N-(2-methoxyethyl)-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2-amine

HRID 82013

Reaktionsgleichung

Reaktionsgleichung von HRID 82013
[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11]([NH:18][C@@H:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH3:20])=[C:12]([NH2:17])[CH:13]=[N:14]3)=[CH:9][C:8]=2[O:27][CH3:28])=[C:5]([CH3:29])[O:4][N:3]=1.[N:30]([CH2:33][CH2:34][O:35][CH3:36])=[C:31]=S.C(Cl)CCl>CCO>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:27][CH3:28])=[CH:9][C:10]3[C:11]4[N:18]([C@@H:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=5)[CH3:20])[C:31]([NH:30][CH2:33][CH2:34][O:35][CH3:36])=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:29])[O:4][N:3]=1

Komponenten

5

Edukt 3

HCID 111,2-DichloroethaneHCID 1234752-Methoxyethyl isothiocyanate2×HCID 672077397-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine

Produkt 1

HCID 665714697-(3,5-dimethylisoxazol-4-yl)-8-methoxy-N-(2-methoxyethyl)-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2-amineAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-N4—((R)-1-(pyridin-2-yl)ethyl)quinoline-3,4-diamine (for a preparation, see Intermediate 25) (538 mg, 1.38 mmol) in EtOH (40 mL) was added 1-isothiocyanato-2-methoxyethane (0.30 mL, 2.76 mmol) and the mixture heated at 60° C. for 5.5 h. A further portion of 1-isothiocyanato-2-methoxyethane (0.15 mL, 1.38 mmol) was added and the reaction mixture heated at 60° C. overnight. The mixture was concentrated in vacuo, the residue dissolved in THF (40 mL), EDC (530 mg, 2.76 mmol) added, and the mixture heated at 60° C. for 4 h. The mixture was concentrated in vacuo and the residue purified by chromatography (100 g column, 2M methanolic ammonia/DCM gradient) to give the crude product which was further purified by MDAP (HpH) to give 7-(3,5-dimethylisoxazol-4-yl)-8-methoxy-N-(2-methoxyethyl)-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2-amine (122 mg, 0.258 mmol, 19% yield) as a white solid. LCMS: (Formate, 2 min), Rt 0.73 mins, MH+ 473.

Aufarbeitung

  1. temperaturethe reaction mixture heated at 60° C. overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in THF (40 mL)
  4. temperaturethe mixture heated at 60° C. for 4 h
  5. concentrationThe mixture was concentrated in vacuo
  6. customthe residue purified by chromatography (100 g column, 2M methanolic ammonia/DCM gradient)
  7. customto give the crude product which
  8. customwas further purified by MDAP (HpH)

Quellen und Nachweise

ORD-Eintrag
ord-766cd23d01984a2f8ab83afa1f17412c
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846709B2

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