4-Toluenesulfonyl chloride → 8-{4-[2-(6-Chloro-1-benzofuran-3-yl)ethyl]-1-piperazinyl}-quinoline

HRID 1178795Notes

Reaction equation

HRID 1178795 reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5]2[C:6]([CH2:9][CH2:10]O)=[CH:7][O:8][C:4]=2[CH:3]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.S(C1C=CC(C)=CC=1)([O-])(=O)=O.[N:36]1([C:42]2[CH:43]=[CH:44][CH:45]=[C:46]3[C:51]=2[N:50]=[CH:49][CH:48]=[CH:47]3)[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C(N(CC)C(C)C)(C)C>N1C=CC=CC=1.CS(C)=O>[Cl:1][C:2]1[CH:13]=[CH:12][C:5]2[C:6]([CH2:9][CH2:10][N:39]3[CH2:40][CH2:41][N:36]([C:42]4[CH:43]=[CH:44][CH:45]=[C:46]5[C:51]=4[N:50]=[CH:49][CH:48]=[CH:47]5)[CH2:37][CH2:38]3)=[CH:7][O:8][C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85570p-ToluenesulfonateHCID 118307868-(1-piperazinyl)QuinolineHCID 236144432-(6-Chloro-1-benzofuran-3-yl)ethanol

Product 1

HCID 114521428-{4-[2-(6-Chloro-1-benzofuran-3-yl)ethyl]-1-piperazinyl}-quinoline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 1049PyridineSolvent

Procedure

To a stirred solution of 2-(6-chloro-1-benzofuran-3-yl)ethanol (980 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 filtered and concentrated. The crude product obtained was taken to next step without any purification. A mixture of tosylate (350 mg. 1 mmol) (obtained by the above mentioned process) and 8-piperazino-quinoline (213 mg, 1 mmol) was heat 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 eluting it initially with 70% ethyl acetate:hexane and then with 5% methanol:ethyl acetate. 8-{4-[2-(6-chloro-1-benzofuran-3-yl)ethyl]-1-piperazinyl}-quinoline was isolated as a yellow oil. Yield: 120 mg (30%); (M+H): 392; 1HNMR (400 MHz, CDCl3):δ 8.82˜8.81 (dd, J1=1.7 Hz, J2=1.7 Hz, 1H); 8.40˜8.20 (dd, J1=1.8 Hz, J2=1.8 Hz, 1H); 7.46˜6.92 (m, 8H); 3.50˜2.70 (m, 12H).

Workup

  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 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 eluting it initially with 70% ethyl acetate

Sources & evidence

ORD record
ord-d6b5f130474946e7b36f94bc09a80ce8
Source dataset
uspto-grants-2007_10
Patent number
US07276603B2

Reaction notes

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