4-Toluenesulfonyl chloride → 8-{4-[2-(1-Benzofuran-3-yl)ethyl]-1-piperazinyl}-6-fluoroquinoline

HRID 1178793

Reaktionsgleichung

Reaktionsgleichung von HRID 1178793
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][CH2:11]O)=[CH:2]1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.S(C1C=CC(C)=CC=1)([O-])(=O)=O.[F:35][C:36]1[CH:37]=[C:38]2[C:43](=[C:44]([N:46]3[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]3)[CH:45]=1)[N:42]=[CH:41][CH:40]=[CH:39]2.C(N(CC)C(C)C)(C)C>N1C=CC=CC=1.CS(C)=O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][CH2:11][N:49]2[CH2:50][CH2:51][N:46]([C:44]3[CH:45]=[C:36]([F:35])[CH:37]=[C:38]4[C:43]=3[N:42]=[CH:41][CH:40]=[CH:39]4)[CH2:47][CH2:48]2)=[CH:2]1

Komponenten

8

Edukt 5

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85570p-ToluenesulfonateHCID 109538362-(Benzofuran-3-yl)ethanolHCID 589754886-Fluoro-8-(piperazin-1-yl)quinoline

Produkt 1

HCID 113832708-{4-[2-(1-Benzofuran-3-yl)ethyl]-1-piperazinyl}-6-fluoroquinoline

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 1049PyridineLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-(1-benzofuran-3-yl)ethanol (815 mg, 5 mmol) in anhydrous pyridine (20 ml), p-toluenesulfonyl chloride (1.14 g, 6.0 mmol) was added. The reaction mixture was kept at 0° C. for 48 hrs and quenched with ice cold water. The reaction mixture was extracted with chloroform, washed well with water, and dried over anhydrous MgSO4. It was then filtered and concentrated. The crude product obtained was taken to next step without any purification. A mixture of tosylate (316 mg. 1 mmol) (obtained by the above mentioned process) and 6-fluoro-8-piperazino quinoline (231 mg, 1 mmol) was heated at 120° C. in DMSO in the presence of N,N-diisopropylethylamine (5 ml, excess) for 24 hrs. At the end, reaction mixture was quenched with water and extracted with chloroform. The organic layer was washed with water and dried over anhydrous MgSO4 and concentrated to dryness. The dark colored solid was purified by silica-gel column chromatography by initially eluting it with 70% ethyl acetate:hexane and then with 55% methanol:ethyl acetate. The product, 8-{4-[2-(1-benzofuran-3-yl)ethyl]-1-piperazinyl}-6-fluoroquinoline, was isolated as yellow oil. Yield: 220 mg (58%); (M+H): 376. 1HNMR (400 MHz, CDCl3):δ 8.82˜8.80 (dd, J1=1.7 Hz, J2=1.7 Hz, 1H), 8.08˜8.03 (dd, J1=1.8 Hz, J2=1.8 Hz, 1H), 7.69˜6.32 (m, 8H), 3.50˜2.63 (m, 12H).

Aufarbeitung

  1. customquenched with ice cold water
  2. extractionThe reaction mixture was extracted with chloroform
  3. washwashed well with water
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationIt was then filtered
  6. concentrationconcentrated
  7. customThe crude product obtained
  8. customwas taken to next step without any purification
  9. customobtained by the
  10. customAt the end, reaction mixture
  11. customwas quenched with water
  12. extractionextracted with chloroform
  13. washThe organic layer was washed with water
  14. dry with materialdried over anhydrous MgSO4
  15. concentrationconcentrated to dryness
  16. customThe dark colored solid was purified by silica-gel column chromatography
  17. washby initially eluting it with 70% ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-31bacf9585734547ad9d8dc5633e9e12
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07276603B2

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