Synthesis of 2-Methyl-2,5-diazabicyclo[2.2.1]heptane, Side Chain to Danofloxacin

Abstract

Various syntheses of the side chain of the quinolone antibiotic danofloxacin are described. The realization that the N-methyl substitution on the side chain 2-methyl-2,5-diazabicyclo[2.2.1]heptane can reside on either nitrogen, due to the symmetry of the molecule, played a major role in the design of the commercial synthetic route.

Asymmetric Synthesis of Silanediol Inhibitors for the Serine Protease Coagulation Cascade Enzyme FXIa

“…Mixing this mesylate with sodium azide in DMF, however, led to cyclization and formation of the proline-alanine-like structure 23 . At 50 °C, this cyclization was complete within 20 min, and even in the absence of sodium azide the cyclization still occurred in DMF but required 6 h. Cyclization of 4-(mesyloxy)-1­( N )-butylsulfonamide structures has been commonly performed, but in all cases these cyclizations involved the use of a base such as potassium carbonate. − While this appears to be a very useful approach to proline-containing silanediol dipeptide analogues, it was not useful for the goals of this study.…”