Synthesis of 3-methyl-1-H-indazole (a)
Synthesis of 3-methyl-1-carbethoxy ethyl indazole (b)
0.25 ml of 1% acetic acid solution was administered intra peritoneally to produce writhing in mice. The severity of pain response (writhing) was assessed by counting the number of wriths (constriction of abdomen, turning of trunk (twist) and extension of hind limbs) in mice. Number of wriths per animal was counted during a 30 minute session beginning 3 minutes after injection of acetic acid. The protective role of synthesized compounds on acetic acid induced writhing was evaluated.
Synthesis of 3-methyl-1-carbethoxy methyl indazole (c)
In summary we report the serendipitous discovery of a new precursor for the one step preparation of indazoles, and crystal structures of oxime 2 and the corresponding indazole 3 that provide clues to the reaction mechanism. The reaction conditions were generalized to afford several examples of the tricyclic pyridazino[1,2-a]indazolium ring system (9-18), and extended to the gram scale synthesis of nigeglanine hydrobromide 1. We note in passing that many of these indazolium ions are fluorescent with colors of blue (9), blue/green (1), and purple (15). As this method quickly affords indazollium analogs of the natural product, their fluorescence may provide an opportunity for cellular imaging studies in the future.
Indazole synthesis - Organic chemistry
In general indazoles, or heterocycles, are synthesized by N–C bond forming reactions but examples of indazoles formed from creating N–N bonds have also been reported. Electrophilic amination of this type has been exploited previously by Hassner and more recently by Stambuli. In both examples an activating agent — DCC in the former and MsCl in the later — was used to promote attack of the oxime nitrogen to form the N–N bond. In our approach, no such activating agent is required.