An Efficient Ugi‐Azide Four‐Component Approach for the Preparation of Novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] Indoles

Abstract

in Wiley Online Library (wileyonlinelibrary.com).The synthesis of novel 1-(1H-tetrazol-5-yl)-10-chloro-1,2,3,4-tetrahydropyrazino[1,2-a] indole derivatives starting from the initially prepared 1-(2-bromoethyl)-3-chloro-1H-indole-2-carbaldehyde is described. A variety of likely biologically relevant pyrazino[1,2-a] indole-based 1,5-disubstituted tetrazoles was obtained in moderate to high yields via an Ugi-azide reaction. These reactions presumably proceed by the imine formation, intramolecular cyclization to iminium ion, and nucleophilic addition tandem reactions, respectively.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…Recently, the Ghandi group developed a metal‐free Ugi‐azide four‐component reaction starting fromindole‐2‐carbaldehyde, benzylamine, sulfonyl hydrazides, NaN 3 and isocyanides at room temperature (Eq. 70‐1).…”

Indole‐2‐Carboxaldehyde: An Emerging Precursor for the Construction of Diversified Imperative Skeleton

“…In 2019, S. Salahi and co-workers reported the synthesis of novel 1-(1H-tetrazol-5-yl)-10-chloro-1,2,3,4-tetrahydropyrazino [1,2-a]indole derivatives from 1-(2-bromoethyl)-3-chloro-1Hindole-2-carboxaldehyde via a one-pot four-component Ugiazide reaction (Scheme 20). [72] The reaction of 1-(2-bromoethyl)-3-chloro-1H-indole-2-carboxaldehyde (131) with benzylamine, tert-butyl isocyanide, and sodium azide in methanol at room temperature afforded the product 132a in 44 % yield. The yield of the product increased to 70 % when the reaction was carried out by stepwise addition of benzylamine in methanol followed by isocyanide and sodium azide.…”

“…Synthesis of novel 1-(1H-tetrazol-5-yl)-10-chloro-1,2,3,4-tetrahydropyrazino[1,2-a]indole derivatives through four-component Ugi-azide reaction of indole-2-carboxaldehydes. [72]…”

Synthesis of bis(1,5‐disubstituted tetrazoles) via double four component Azido‐Ugi reaction

“…Because they are abundant in the structure of active drug compounds. [5][6][7][8][9] For example, Cilostazol (A) as an antiinflammatory, Pentylenetetrazol (B) as a circulatory and respiratory stimulant, Nojiritetrazole (C) as an antidiabetic, Cefmetazol (D) and Latamoxef (E) as an antibiotic, are drugs having the 1,5-DT cores (Figure 1). Also, 1,5-DTs have a substantial interest in drug discovery programs, because tetrazole group is an amide bond isosteres.…”