Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[CH2:9][S:8][CH2:7]1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].[Br-]>[Na+].[I-].CO.C(Cl)(Cl)Cl.CC#N>[F:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:24][CH2:23][N:22]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10](=[O:11])[CH2:9][S:8][CH2:7]3)[CH2:21][CH2:20]2)=[CH:17][CH:18]=1A mixture of 3-(4-bromobutyl)-4-thiazolidinone (4.01 g), 1-(4-fluorophenyl)piperazine (3.35 g), K2CO3 (4.64 g), NaI (150 mg) and CH3CN (150 ml) was heated at 100° C. (bath temperature) under N2 for 18 h. TLC analysis (silica gel, 8% MeOH/CHCl3) showed one major product at Rf =0.36, and the absence of starting bromide. The reaction mixture was cooled to room temperature and concentrated in vacuo to an oil which was taken up in EtOAc. The mixture was filtered to remove the precipitate and the filtrate concentrated in vacuo to an amber oil which solidified under vacuum. The solid (5.86 g) was dissolved in CHCl3 and flash chromatographed (silica gel) and thereafter recrystallized from hexane/CH2Cl2 to yield in two crops 3.93 g of white crystals, mp 83°-85° C. TLC analysis showed a trace of slower moving impurity. Recrystallization from hexane/CH2Cl2 afforded 3.1 g of white needles which were still slightly impure by TLC. The material was again flash chromatographed (silica gel) and recrystallized from hexane/CH2Cl2 to give 2.67 g of pure product, mp 84°-85° C.
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