4-Toluenesulfonyl chloride → 2,3-Dioxoindoline-5-sulfonyl chloride

Beteiligte Stoffe

Reaktionsschritte

The synthesis of 5-(2-phenoxymethylpyrrolidine-1-sulfonyl)isatin analogues is shown in Scheme 1 (FIG. 5). The 5-chlorosulfonylisatin 6 was prepared by reaction of 5-isatinsulfonic acid, sodium salt hydrate (5) with phosphorus oxychloride in tetramethylene sulfone at 60° C. for 3 h. The hydroxyl group of N-Boc-2-pyrrolmethanol (7) was first tosylated with p-toluenesulfonyl chloride in pyridine to give compound 8, followed by displacement of the tosylate group by sodium phenoxide in DMF to afford N-Boc-2-(phenoxymethyl)pyrrolidine 9. The N-Boc group of 9 was removed with TFA, and the secondary amine was coupled with 6 in THF using triethylamine as an acid scavenger to afford the 5-(2-phenoxymethyl-pyrrolidinesulfonyl)-1H-2,3-dione 10 in 84% yield. The isatin nitrogen was alkylated by treatment of 10 with sodium hydride in DMF at 0° C. followed by addition of various alkyl halides to give compounds 2 and 11a-e,g-i. Compound 11f was prepared by hydrolysis of 11e with sodium hydroxide in aqueous methanol.

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