Potassium Iodide → 5-{3-[4-(5-Cyanoindol-3-yl)-1,2,5,6-tetrahydropyrid-1-yl]propoxy}-2-methylbenzothiazole

HRID 1016506

Reaktionsgleichung

Reaktionsgleichung von HRID 1016506
[CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14]Cl)=[CH:7][C:5]=2[N:6]=1.[C:16]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[C:21]2[C:27]1[CH2:28][CH2:29][NH:30][CH2:31][CH:32]=1)#[N:17].[I-].[K+]>C(#N)C.O.[OH-].[NH4+].C(OCC)(=O)C>[C:16]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[C:21]2[C:27]1[CH2:28][CH2:29][N:30]([CH2:14][CH2:13][CH2:12][O:11][C:8]2[CH:9]=[CH:10][C:4]3[S:3][C:2]([CH3:1])=[N:6][C:5]=3[CH:7]=2)[CH2:31][CH:32]=1)#[N:17]

Komponenten

8

Edukt 3

HCID 4875Potassium IodideHCID 113335543-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrileHCID 184070592-Methyl-5-(3-chloropropoxyl)-benzothiazole

Produkt 1

HCID 102028485-{3-[4-(5-Cyanoindol-3-yl)-1,2,5,6-tetrahydropyrid-1-yl]propoxy}-2-methylbenzothiazoleAusbeute 37,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 14923Ammonium HydroxideLösungsmittel

Versuchsvorschrift

A mixture of 2-methyl-5-(3-chloropropoxyl)-benzothiazole (3 g, 12.4 mmol), 5-cyano-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (3 g, 13.4 mmol) and a catalytic amount of potassium iodide in 50 ml of acetonitrile was stirred at 80° C. overnight. The reaction mixture was cooled, diluted with water, ammonium hydroxide and ethyl acetate. The two phases were separated and the aqueous phase was extracted with ethyl acetate twice. The organic phases were combined, washed with brined, dried over sodium sulfate and then concentrated under reduced pressure to a solid. This residual solid was subjected to a silica gel chromatography, eluting with 7% methanol in dichloromethane. Fractions shown to contain product were combined and concentrated to provide 2 g of the title compound in 35% yield as free base. The resulting free base was dissolved in methanol/dichloromethane and precipitated with excess HCl in ether. Recrystalization from ethanol give 1.8 g of the title compound as a light yellow solid. mp. 263-65° C. MS(CI) m+1=429. EA (C25H24N4 OS.1.7HCl): Theory: C, 61.21%; H, 5.28%; N, 11.42%. Found: C, 61.10%; H, 5.43%; N, 11.39%.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. customThe two phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate twice
  4. washwashed with brined,
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure to a solid
  7. washeluting with 7% methanol in dichloromethane
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1a07a0b309bc413491f7967027a90f80
Quelldatensatz
uspto-grants-2002_11
Patentnummer
US06476051B2

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