Regiospecific Synthesis and Structural Studies of 3,5-Dihydro-4-pyrido[2,3-][1,4]diazepin-4-ones and Comparison with 1,3-Dihydro-2-benzo[][1,4]diazepin-2-ones.

Nine 3,5-dihydro-4-pyrido[2,3-][1,4]diazepin-4-ones (-), some of which contain fluoro-substituents, have been regiospecifically prepared by reaction of 2,3-diaminopyridines with ethyl aroylacetates. In two cases, open intermediates have been isolated and these are related to the reaction pathway. The X-ray crystal structure of 1-methyl-4-phenyl-3,5-dihydro-4-pyrido[2,3-][1,4]diazepin-4-one () has been solved (formula, CHNO; crystal system, monoclinic; space group, 2/). This is an asymmetric unit constituted by a single nonplanar molecule and its conformational enantiomer due to the presence of the seven-membered diazepin-2-one moiety, which introduces a certain degree of torsion in the adjacent pyridine ring. The H, C, N, and F NMR spectra were obtained and the chemical shifts, together with those of the previously published 1,3-dihydro-2-benzo[][1,4]diazepin-2-ones (-), i.e., a total of 544 values, were successfully compared with the chemical shifts calculated at the gauge invariant atomic orbital (GIAO)/Becke, three-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,p) level. The seven-membered ring inversion barrier in 5-benzyl-2-phenyl-3,5-dihydro-4-pyrido[2,3-][1,4]diazepin-4-one () was determined and, in conjunction with the data from the literature, compared with the B3LYP/6-311++G(d,p) computed values. This allowed the determination of several structural effects. The rotation about the exocyclic N1-CR bond was also calculated and its dynamic properties were discussed.