Syntheses of 11-substituted 3-methyl-3,4,10,11-tetrahydro-1H,5H-pyrano[4, 3-b][1,5]benzodiazepin-1-ones.

In the course of our synthetic studies on biologically active compounds using dimedone, tetronic acids, and tetramic acids,1) we reported that some 10-substituted 3,3-dimethyl3, 4, 9, 10tetrahydro1Hfuroand -pyrrolo [4, 3-b] [1, 5] benzodiazepin1-ones (1 and 2) showed analgesic activity as strong as that of aminopyrine in the phenylquinone writhing test in mice.2) Namely, the extents of inhibition were 56.1% with la, 61.0% with lb, and 68.3% with 2 at the dose of 50 mg/kg p.o., while that of aminopyrine was 66.2%. The above observations prompted us to synthesize benzodiazepinone derivatives fused with other heterocyclic compounds in order to test their analgesic activity. We therefore synthesized 11-substituted 3methyl3, 4, 10, 11tetrahydro1H, 5Hpyrano [4, 3-b] [1,5] benzodiazepin1ones (6), which are isomers of 1, and investigated the structure-activity relationships. Synthesis of pyranobenzoidiazepinones (6) was performed by using a method similar to that employed previously for the preparation of furobenzodiazepinone derivatives (1).3) Thus, the enaminolactones (5a and 5b) were prepared by boiling a benzene solution of 3-hydroxy-5methyl2penten5olide (3)4) and an equimolar amount of 1, 2diaminobenzene (4a) or 1,2diamino-4-chlorobenzene (4b) in 85.1 and 39.9% yields, respectively. When ethanol solutions