Azabicyclo chemistry. 6. An investigation of one of the chemical parameters for analgetic activity. Synthesis of 2-methyl-2-azabicyclo[3.3.1]non-6-ene and -non-7-ene

Abstract

The olefins 2-methyl-2-azabicyclo[3.3.1]non-6-ene (3) and -non-7-ene (6) were prepared in order to evaluate their analgetic activity. The reduction of 2-methyl-2-azabicyclo[3.3.1]nonan-7-one (4) with NaBH4 gave, stereospecifically, the axial alcohol 5. Reaction of 5 with CH3SO2Cl-pyridine gave directly the olefins 3 and 6, both of which upon hydrogenation gave the known 2-methyl-2-azabicyclo[3.3.1]nonane (7). The structural proof of 3, 5, and 6 was ascertained by spectral methods. Of the compounds prepared, 3, 5, and 6 were essentially inactive as analgetics when tested in mice by the hot-plate method, while 4 had marginal activity.

Synthesis and analgetic activity of some benzomorphan analogs

“…Anal. (8). To a stirred solution of 7 (1.3 g, 5.3 mmol) in C6H8 (100 mL) and THF (25 mL) was added Br2 (0.85 g, 5.3 mmol) in THF (10 mL) at room temperature during 30 min.…”