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Pyrrolo[2,1‐ c ][1,4]benzoxazepines. 2 . Synthesis of 5‐phenyl derivatives
Author(s) -
Kapples Kevin J.,
Effland Richard C.
Publication year - 1993
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570300132
Subject(s) - chemistry , formylation , sodium methoxide , dimethylamine , medicinal chemistry , acetylide , sodium borohydride , acylation , pyrrole , ketone , nucleophile , methanol , organic chemistry , catalysis
A series of 5‐phenylpyrrolo[2,1‐ c ][1,4]benzoxazepines with basic substituents at the 11‐position has been synthesized utilizing a nucleophilic aromatic fluoride displacement‐cyclization. Piperidinyl derivatives were prepared by Vilsmeier formylation of the key 1‐[(2‐fluorophenyl)phenylmethyl]pyrrole ( 4 ) followed by addition of a piperidinyl Grignard reagent and cyclization of the resulting carbinol. A (dimethylamino)methyl derivative was prepared via an analogous cyclization of α‐(dimethylamino)methyl‐1‐[(2‐fluorophenyl)phenyl‐methyl]‐1 H ‐pyrrole‐2‐methanol ( 10 ), obtained by the Hoeben‐Hoesch acylation of 4 with chloroacetonitrile, addition of dimethylamine to the resulting α‐chloroketone 8 , and reduction of the α‐(dimethylamino)ketone 9 with sodium borohydride to give 10 .