Tetrahedron Letters,Vo1.24,No.44,pp 4789-4792,1983 0040-4039/83 $3.00 +.OO Printed in Great Britain 61983 Pergamon Press Ltd. A NOVEL APPROACH TOWARDS THE SYNTHESIS OF THE 3,4,5- TRIHYDRO-1,3-DIAZEPIN-5-OL RING STRUCTURE

Abstract: A catalytic reduction of the nitrile portion of the trimethylsilyl cyanohydrin 7 to a primary amine has produced an in situ annulation to generate the 3,4,5-trihydro-1,3-diazepin-5-01 ring. This ring substructure has demonstrated important biological significance.3 Our efforts directed towards the synthesis of potential inhibitors of the enzyme adenosine deaminase have yielded a new and novel method for the formation of a 3,4,5-trihydro-1,3-diazepin-5-01 ring (Figure 1, in brackets) fused to another heterocyclic ring. A bicyclic heterocyclic ring system containing the 3,4,5-trihydro-1,3-diazepin-5-01 structure fused to an imidazole ring is shared by the nucleoside antibiotics 2'-deoxycoformycin (l_, pentostatin') and coformycin2 (21, both potent inhibitors of adenosine deaminase.3 Figure 1. I, R = H; pentostati