Triazine-fused β-carbolines: a facile three-step, one-pot synthesis of novel 2-alkyl(aryl)amino and 2-dialkylamino-7H-[1,3,5]triazino [1',2':1,6]pyrido[3,4-b]indol-4-ones

Abstract

Triazine-fused β-carbolines: a facile three-step, one-pot synthesis of novel 2-alkyl(aryl)amino and 2-dialkylamino- [3,4-b]indol-4-ones is presented. The construction of these compounds was achieved by one-pot synthesis involving condensation of 3-amino-β-carbolines with ethoxycarbonyl isothiocyanate followed by amination of the resulting thioureas and finally thermal ring closure of the resulting guanidines which allowed access to the unreported title heterocycles.Keywords: Triazinopyridoindoles, fused β-carbolines, triazino-β-carbolines, 2-aminotriazino-β-carbolines, cyclization IntroductionThe β-carboline skeleton is common in the structure of many natural and synthetic products associated with a broad spectrum of biological activities and pharmaceutical properties including sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic, and antimicrobial activities 1-7 as well as phosphodiesterase (PDE5) However, to the best of our knowledge, no reports have appeared concerning the synthesis of 1,3,5-triazino-β-carbolines. Thus it was deemed of interest to find a facile and efficient methodology to synthesize this hitherto unknown annulated β-carboline ring system. The presumed co-planarity and linearity of this fused polyheterocyclic system could in addition favour DNA intercalation and potentially provide anticancer compounds.Recently, Demeunynck et al. 21published a synthetic route to the 2-alkylaminoquinolino[2,3-f]quinazolin-1-one skeleton from 3-aminoacridine 1 (Scheme 1). The authors followed Manimala and Anslyn's methodology, 22 by condensing the aminoacridines with ethoxycarbonyl isothiocyanate followed by coupling with aliphatic amines and deprotection of the guanidine function. The authors noted that the ethoxycarbonyl group of the N-protected guanidino intermediates was ideally positioned to react by intramolecular Friedel-Crafts type substitution to form, in one step, the fused pyrimidinone ring of 3 (Scheme 1). The same paper 21 also described a two-step methodology for the synthesis of substituted 2-propylaminoquinazolin-4(3H)-ones 6 from simple aromatic or heteroaromatic amines 4 (Scheme 2). The preparation of the ethoxycarbonyl guanidines 5 was performed in one pot by careful control of the stoechiometry of the reagents successively added to the chosen aromatic amine dissolved in CH 2 Cl 2 . In most cases, the resulting protected guanidines 5 were easily isolated with excellent levels of purity by simple precipitation from water.

Synthesis of β-Carbolines through Tetra-n-butylammonium Bromide-Mediated Cycloaromatization Reaction of N-Methylaniline with Tryptophan Derivatives

“…m.p. 225～227 ℃; 4, 137.9, 137.2, 134.1, 129.1, 127.9, 122.7, 121.3, 120.7, 118.0, 112.8, 61.0, 14.8 indole-3-carboxylate (3d): [24] White solid (26.7 mg, 41%) 8, 141.4, 137.6, 136.8, 133.9, 132.9, 126.9, 123.7, 120.5, 119.7, 117.6, 112.0, 51.9 4, 142.0, 138.2, 137.5, 134.5, 133.5, 127.5, 124.3, 121.0, 120.3, 118.2, 112.6, 52.5 indole-3-carboxylate (3f): [25] White solid (25.2 mg, 33%). m.p.…”

A Facile Three-Steps, One-Pot Synthesis of Novel 2-Alkylamino and 2-Dialkylamino-4H-Pyrido[1,2-A][1,3,5] Triazin-4-Ones from 2-Aminopyridine and 2-Aminopicolines

“…i) SCN-CO2Et, DMF, rt, 2h ii) HNRR', HgCl2, DMF, 0 -5°C then rt, 4h iii) quasi one-pot: HCl, dioxane. iii) one-pot: DMF, 80°C, 2h Primas et al [12] have recently studied one pot syntheses of pyrimidocarbazole starting from 3-aminocarbazoles. In another paper, the same authors [13] described a three-steps methodology, one pot synthesis of novel 2-alkyl(aryl)amino and 2dialkylamino-7H-[1, 3,5]triazino [3,4-b] pyridoilndol-4-one andderivatives starting 3-amino-β-carbolines in similar conditions to our work [14].…”