Formation of - and -Fused Systems

To suppress enamine-derived side products, we explored addition of benzotriazole (BtH) to the reaction mixture. The premise behind these experiments was the ability of BtH to form stable adducts with imines, thereby blocking tautomerization of 19 to 20 through in situ formation of the benzotriazolyl derivative 21. It was hoped that subsequent hydride displacement of the Bt moiety would afford the desired mono alkylated products 23. Indeed, analytical high-performance liquid chromatography (HPLC) revealed a remarkable improvement in terms of product purity, especially for reactions carried out at room temperature, with the desired secondary anilines 23 being essentially the only products detected. In 

In the case of 31, slightly harsher conditions were required to drive the nucleophilic aromatic substitution to completion, so the reaction was car- 

In the case of the series derived from homocysteine 32, the critical transformation proved to be formation of the eight-membered ring. This was successful only if the aniline nitrogen was present in its nonalkylated form. Thus the synthetic efforts were restricted to the amide alkylation 

Given their impressive therapeutic activities, it is not surprising that benzodiazepines were among the first small molecules to be synthesized on solid support.The main synthetic interest, however, has so far focused on 

Preliminary experiments using P-amino acids as S yAr nucleophiles showed that they either completely failed to react or afforded product mixtures, due to their poor solubility in nonaqueous solvents, p-Amino acid esters, on the other hand, are readily soluble in DMF, but only a few are commercially available. In this section, two different approaches are described that have successfully circumvented these problems. The key features are (i) a novel aqueous solvent system allowing the use of free a- and 

90 BENZOFUSED HETEROCYCLES VIA SOLID-PHASE SWAR REACTIONS 

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