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A Novel Rearrangement of Cyclic Glutamine Derivatives: Ring Contraction in 3,6‐Diamino‐2,3,4,5‐tetrahydropyridin‐2‐ones to Yield 5‐Iminoproline Amides
Author(s) -
Belov Vladimir N.,
Sokolov Viktor V.,
Zlatopolskiy Boris D.,
de Meijere Armin
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100404
Subject(s) - chemistry , amide , yield (engineering) , stereochemistry , bicyclic molecule , derivative (finance) , proline , hydrolysis , ring (chemistry) , glutamine , medicinal chemistry , organic chemistry , amino acid , biochemistry , financial economics , metallurgy , materials science , economics
A new rearrangement of the cyclic L ‐glutamine derivative( S )‐6‐carbamoylamino‐3‐(methylamino)‐2,3,4,5‐tetrahydropyridin‐2‐one ( 2 ) and its descarbamoyl analogue 10 ‐H was found to yield enantiomerically pure 5‐carbamoylimino‐1‐methyl‐ L ‐proline amide ( 12 ‐CONH 2 ) and its descarbamoyl analogue 12 ‐H, respectively. Cyclic amidines 2 and 10 ‐H were generated from the amide N 2 ‐ZGlnOEt 3 in seven and six steps, respectively. Deprotection of ( S )‐6‐amino‐3‐[( N ‐benzyloxycarbonyl‐ N ‐methyl)amino]‐2,3,4,5‐tetrahydropyridin‐2‐one ( 8 ) led directly to 5‐iminoproline amide 12 ‐H (via 10 ‐H and the bicyclic orthoamidine 11 ‐H) in 66 % overall yield from 3 . Carbamoylation of 8 with ZNCO (Z = PhCH 2 OCO) followed by hydrolytic removal of both Z groups gave 5‐(carbamoylimino)proline amide 12 ‐CONH 2 (via 2 and orthoamidine 11 ‐CONH 2 ) in 70 % overall yield from 3 .