Eighteen novel pyrimido [4,5e] [ 1,4]oxazepin-5-ones were prepared directly via the reaction of either ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate (Ia) or ethyl 4-chloro-2-m-chlorophenyl-5-pyrimidinecarboxylate (Ib) with a variety of substituted 2-(alkylamino)ethanoIs. A typical example was the preparation of 8,9-dihydro-9-methyl-2-phenylpyrimido[ 4,5-e] [ 1,4]oxazepin-5(7H)-one (IIa) from the reaction of Ia with 2-(methy1amino)ethanol. Hydrolytic cleavage of the lactone ring in IIa with sodium hydroxide solution, followed by acidification with hydrochloric acid afforded 4-[(2-hydroxyethyl)methylamino]-2-phenyl-5-pyrimidinecarboxylic acid (19. Reactions of IIa with concentrated ammonium hydroxide or hydrazine also caused cleavage of the lactone ring, giving the corresponding amide (V) or hydrazide (VI), respectively. Structural assignments were supported by infrared and nuclear magnetic resonance spectra.Previously, we reported on the use of ethyl 4-chloro-2phenyl-5-pyrimidinecarboxylate (Ia) and related derivatives as intermediates for the preparation of several condensed pyrimidine systems (la-d). Further interest in the chemistry and general pharmacologic action of such structural types prompted additional work in this area. As a result of that effort we now report the preparation of a new heterocyclic class, the pyrimido[4,5e] [ 1,4] oxazepin-5ones (IIa-r) obtained directly via the reaction of Ia-b with a variety of substituted 2-(alkylamino)ethanoIs (2,Za).In a typical example, treatment of Ia with 2-(methylamino)ethanol in refluxing ethanol containing sodium carbonate gave the lactone 8,9-dihydro-9-methyl-2-phenyl- pyrimido[4,5-e] [ 1,4]oxazepin-5(7H)-one (IIa, Scheme I).The possibility that the reaction afforded instead, the isomeric lactam 111, was considered unlikely on the basis of the infrared carbonyl absorption, which appeared at 5.88 p. A similar lactone, l-methyl-2,3-dihydro-4,1benzoxazepin-5( lH)-one, has its carbonyl absorption at 5.86 / . A (3). The lactam carbonyl band for 111 might be SCHEME I 0 0