合成路线1

Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II), which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III). The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV). 1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII). Finally, intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.

合成路线2

The Friedel Crafts condensation of 6-chloroindolin-2-one (I) with 14C labeled 2-chloroacetyl chloride (II) by means of AlCl3 in CS2 gives 6-chloro-5-(2-chloroacetyl)indolin-2-one (III), which is reduced with trimethylsilane in TFA to yield the labeled chloroethyl derivative (IV). Finally, this compound is condensed with 3-(1-piperazinyl)-1,2-benzoisothiazole (V) by means of Na2CO3 in refluxing water to provide the target radiolabeled compound.

合成路线3

The bromination of 3-chloro-1,2-benzoisothiazole (I) with Br2 in AcOH using FeCl3 as catalyst gives a mixture of 3,5-dibromo-1,2-benzoisothiazole (II) and 3,7-dibromo-1,2-benzoisothiazole (III) that are separated by flash chromatography. The desired isomer (III) is condensed with piperazine (IV) in refluxing diglyme to yield 7-bromo-3-(1-piperazinyl)-1,2-benzoisothiazole (V), which is condensed with 6-chloro-5-(2-chloroethyl)indolin-2-one (VI) by means of Na2CO3 in refluxing water to afford the brominated adduct (VII). Finally, this compound is debrominated with tritium gas over a Pd/BaSO4 catalyst in THF to provide the target radiolabeled compound.

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合成路线6