A Practical, Metal-Free Synthesis of 1H-Indazoles

Abstract

The synthesis of 1H-indazoles is achieved from o-aminobenzoximes by the selective activation of the oxime in the presence of the amino group. The reaction occurs with a variety of substituted o-aminobenzoximes using a slight excess of methanesulfonyl chloride and triethylamine at 0-23 degrees C and is amenable to scale-up. The synthesis of 1H-indazoles under these conditions is extremely mild compared with previous synthetic approaches and affords the desired compounds in good to excellent yields.

Ruthenium‐Catalyzed Direct CH Amidation of Arenes Including Weakly Coordinating Aromatic Ketones

“…It is also noteworthy that synthetic utility of ortho-amido aryl ketone products is significant, and a wide range of bioactive heterocycles could be synthesized by simple conventional methods (Scheme 4). [21] In fact, synthetic procedures are known for the preparation of oxcarbazepines, indazoles, (oxy)indoles, and quinoline derivatives by starting from a common precursor, ortho-amido aryl ketones, and some examples are demonstrated herein. In summary, we have presented the inexpensive ruthenium-catalyzed direct sp 2 CÀH amidation of arenes by using sulfonyl azides as the nitrogen source.…”

N–N Bond-Forming Cyclization for the One-Pot Synthesis of N-Aryl[3,4-d]pyrazolopyrimidines

“…It has previously been reported that only E -oximes can undergo N–N bond-forming cyclizations with amines to give 5-membered aromatic rings. 10 The nitrile byproduct 5 was isolated in 36% yield, presumably as a result of elimination of the O -mesyl- Z -oxime isomer intermediate, since this isomer could not undergo cyclization to form the desired product. 11 …”

Synthesis of indazole motifs and their medicinal importance: An overview

“…The synthesis of 1H-indazoles from ortho-amino benzoximes with creation of the N-N bond has been reported by Canceller et al [26]. This reaction indicate the selective activation of the oxime group by reaction with a slight excess of methane sulfonyl chloride followed by cyclization to the 1H-indazoles by exposure to triethylamine (Scheme-12).…”