Indazole assembly

A similar theme was used by Pabba in the synthesis of indazoles via a one-pot and two-step condensation-arylation sequence [97]. Here Cu(I) catalysis was used to assemble aryl hydrazines with 2-halobenzaldehydes or 2-halo-acetophenones to deliver the target molecules in high yields after two short... 

Qeavage of the A "-Dde and N"-l-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl groups is performed with 2% anhydrous hydrazine or hydrazine hydrate in DMF at room temperature (on resin, 3 x 2min). This leads to a l,5,6,7-tetrahydro-4//-indazol-4-one 25 as the byproduct (Scheme 10), which can be monitored by UV spectroscopy at 220 or 290 nm.O Since hydrazine will also remove Fmoc groups, the assembly of the peptide by Fmoc/tBu chemistry must be completed prior to the cleavage of the Dde or l-(4,4-dimethyl-2,6-diox-ocyclohexyhdene)-3-methylbutyl groups. 

Indazoles may be assembled via thermolysis as well. Treatment of diphenylcarbamoyl chloride with sodium azide gives rise to diphenyl-carbamoyl azide. Thermolysis of the diphenyl-carbamoyl azide then afforded indazolol. Subsequent alkylation of the indazolol then produced a series of indazole derivatives as activators of the nitric oxide receptor, soluble guanylate cyclise. 

Latterly, Reddy et al. reported a novel three-component assembly of 2//-indazoles catalyzed by Cu(II)-HT (Prasad et al., 2013). Through consecutive condensation, and C-N and N-N bond formation processes, the domino reactions of 2-bromobenzal-dehydes, primary amines, and sodium azide smoothly gave the desired 2//-indazole derivatives (Scheme 4.59). The heterogeneous catalyst could be readily recovered and reused several times without significant loss of activity. 

Abstract Some newly developed methods for assembling N-containing heterocycles are summarized here. The key transformations in these methods are Pd- or Cu-catalyzed N-arylation and N-vinylation. The heterocycles include indoles, benzimidazoles, pyrroles, indazoles, indolines, lactams, quinazoUnones and heterobenzazepines. These conceptually-novel and rehable methods should find applications in the synthesis of bioactive compounds and material molecules. 

---