B. Wunsch et al., NONCOMPETITIVE NMDA ANTAGONISTS - A NOVEL SYNTHESIS OF 1-PHENYLTETRAHYDRO-3-BENZAZEPINES, Archiv der pharmazie, 330(7), 1997, pp. 211-214
The key step in the synthesis of the pharmacologically interesting 1-p
henyltetrahydro-3-benzazepine skeleton is the Michael addition of (2-l
ithiophenyl)acetaldehyde acetals, which are generated in situ upon tre
atment of the bromo acetals 5a,b with n-butyl-lithium, to beta-nitrost
yrene (6). The reductive ring closure of the nitro acetals 7a,b succee
ded with zinc dust and hydrochloric acid to give the 3-benzazepines 11
a,b in good yields. The unsubstituted 3-benzazepine 11a showed a consi
derable affinity for the phencyclidine binding site of the NMDA recept
or (K-i = 6.41 mu M), whereas donor substituents in the aryl moiety (1
1b,c) reduce the affinity for the NMDA receptor.