[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH2:24])[CH2:12][CH2:11]2)=[N:2]1.[Na].[CH2:26]=[O:27]>CO.O>[OH-:27].[NH4+:2].[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][CH3:26])[CH2:12][CH2:11]2)=[N:2]12-[2-(4-1,2-Benzisothiazol-3-yl-piperazin-1-yl)-ethyl]-phenylamine (6.76 g, 20.0 mmol) was added to a suspension of sodium metal (2.3 g, 100 mmol) in methanol (30 mL) at rt. The resulting solution was then added to a suspension of paraformaldehyde (0.84 g) in methanol (20 mL). Suspension was warmed to reflux for 4 h. Reaction was cooled to room temperature followed by a careful quench with water (100 mL) and concentration of resulting suspension. The crude was diluted with water (100 mL) and extracted with methylene chloride (150 mL). The extract was dried over magnesium sulfate, filtered and concentrated to brown oil. The crude mixture was purified via medium pressure liquid chromatography using a 300 g silica gel Biotage cartridge eluting with a gradient of methylene chloride to (100:8:1) methylene choride: ethanol: ammonium hydroxide to yield pure {2-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)-ethyl]-phenyl}-methyl-amine as an oil (3.73 g). Yield 53%;
Loading…
