The Knoevenagel condensation of arylacetonitriles with ethyl 4,6-dichloro-3
-formyl-1H-indole-2-carboxylate (2), followed by hydrolysis, provides a con
venient entry into a series of analogs of MDL 105,519, 1, a selective glyci
ne site N-methyl-D-aspartate (NMDA) receptor antagonist. Surprisingly, the
hydrolysis of the indole arylpropenenitriles terminates at the formation of
the corresponding carboxamide and does not proceed further to the desired
dicarboxylic acid. However, when the aryl substituent is pyridine, hydrolys
is proceeds via an azepinoindole unique to this, series, which upon further
hydrolysis converts smoothly to the desired dicarboxylic acid analog. (C)
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