Synthesis of substituted methylidenepyrimidobenzothiazolones as potential cytotoxic agents

Abstract

A range of biologically important substituted 3-methylidene-2,3-dihydro-4H-pyrimido[2,1-b][1,3]benzothiazol-4-ones and 3-methylidene-3,4-dihydro-2H-pyrimido[2,1-b][1,3]benzothiazol-2-ones was synthesized applying Horner-Wadsworth-Emmons methodology for the introduction of exo-methylidene bond onto a heterocyclic ring. Crucial in this approach, phosphonates were prepared by the reaction of ethyl 2-diethoxyphosphoryl-3-methoxyacrylate or ethyl 2-diethoxyphosphoryl-3-chloroacrylate with 2-aminobenzothiazoles, followed by addition of Grignard reagents to the obtained 3-diethoxyphosphoryl-4H-pyrimidobenzothiazol-4-ones or 3-diethoxyphosphoryl-2H-pyrimido[2,1-b][1,3]benzothiazol-2-ones, respectively. Surprising, ambident behavior of 2-aminobenzothiazoles towards ethyl 2-diethoxyphosphoryl-3-methoxyacrylate and ethyl 2-diethoxyphosphoryl-3-chloroacrylate is also discussed.

Synthesis of pyrimido[2,1-b][1,3]benzothiazoles and [1,3]benzothiazolo[3,2-a]quinazolines via one-pot three-component reactions from 2-aminobenzothiazole, arylglyoxals and 1,3-dicarbonyl compounds

“…18 Moreover, organic and medicinal chemists have developed a series of multicomponent reactions (MCRs) for the synthesis of heterocyclic compounds and complex biologically-active compounds, [19][20] such as multi-component reaction of 2-aminobenzimidazole, benzaldehyde derivatives, and active methylene compounds, 6,[21][22] and various other methods. [23][24][25][26][27][28][29] However, some of these modern methods have significant limitations such as tedious workup procedures, low yields, and longer reaction times. Therefore, a new and efficient method for synthesis of pyrimido[2,1-b]- [1,3]benzothiazole and [1,3]benzothiazolo [3,2-a]quinazoline derivatives remains an attractive goal.…”

Topology of Ladder Supramolecular Assemblies in Azahetorocyclic Phosphonates: A Structural and Computational Approach

“…Synthesis and NMR data of diethyl (4-oxo-4H-benzo [4,5]thiazolo[3,2-a]pyrimidin-3-yl)phosphonate 1 were reported previously. 48 Synthetic procedure of 2 and 3: to a solution of 2-amino-6-methoxybenzothiazole or 2-amino-6-chlorobenzothiazole (10.0 mmol) in ethanol (50 mL), 2-diethoxyphosphoryl-3-methoxyacrylate (2.66 g, 10.0 mmol), was added and the mixture was stirred for 24 h. Next, the methanol was evaporated, and Dowtherm A (150 mL) was added. The mixture was heated under reflux for 30 min.…”