Pyridine → 5-Chloro-3-(2-methoxyphenyl)-3-(4-pyridin-3-yl-piperazin-1-yl)-1,3-dihydro-indol-2-one

HRID 1970851Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1970851
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2(O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[O:28][CH3:29].[CH:31]([N:34](CC)[CH:35]([CH3:37])C)([CH3:33])C.ClC1C2C(=CC=CC=2)[NH:43]C1=O>ClCCl.ClCCl.C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[O:28][CH3:29])[N:43]1[CH2:37][CH2:35][N:34]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:31][CH2:33]1

Komponenten

8

Edukt 5

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 124185093-Chloro-1,3-dihydro-2H-indol-2-oneHCID 219059555-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-one

Produkt 1

HCID 689063595-Chloro-3-(2-methoxyphenyl)-3-(4-pyridin-3-yl-piperazin-1-yl)-1,3-dihydro-indol-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 21919333Tetrahydrofurane dichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Pyridine (0.18 mL, 2.24 mmol) and thionyl chloride (0.16 mL, 2.24 mmol) were added to a solution of 5-chloro-3-hydroxy-3-(2-methoxyphenyl)-1,3-dihydro-indol-2-one (WO 2005/030755, 0.50 g, 1.73 mmol) in dichloromethane (40 mL) with ice cooling, and stirred for 45 min at 0° C. The reaction solution was quenched with water, while stirring, and the preparation was extracted with dichloromethane. The organic phase was washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated at reduced pressure. N,N-diisopropylethylamine (0.81 mL, 4.66 mmol) and 1-pyridin-3-yl-piperazine, HCl salt (0.34 g, 1.73 mmol) were added to a solution of the 3-chloro-oxindole intermediate thus obtained in dichloromethane/THF (20 mL) and the reaction mixture was stirred for 12 h at room temperature. The reaction mixture was concentrated at reduced pressure and the residue was distributed between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate again. The combined organic phase was dried over sodium sulphate and concentrated at reduced pressure, and was used further without additional purification. Yield: 0.62 g.

Aufarbeitung

  1. customThe reaction solution was quenched with water
  2. stirringwhile stirring
  3. extractionthe preparation was extracted with dichloromethane
  4. washThe organic phase was washed with water and saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated at reduced pressure
  7. stirringthe reaction mixture was stirred for 12 h at room temperature
  8. concentrationThe reaction mixture was concentrated at reduced pressure
  9. extractionThe aqueous phase was extracted with ethyl acetate again
  10. dry with materialThe combined organic phase was dried over sodium sulphate
  11. concentrationconcentrated at reduced pressure
  12. customwas used further without additional purification

Quellen und Nachweise

ORD-Eintrag
ord-cfb23870a9f240cfbd0036639fafbb40
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431567B2

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