Synthesis of 2-aminothiazole derivatives

Abstract

The optimum amount of urea for the selective bromination of ketones in DMF has been established. The obtained a-bromoketones have been used for the synthesis of 2-aminothiazoles in situ. A series of compounds with potential biological activity has been synthesized proceeding from chloroacetyl derivatives of 2-aminothiazoles.Various 2-aminothiazole (2-AT) derivatives were reported to exhibit biological activity, including antimicrobial [1], antiviral [2], and psychotropic properties [3]. The acetyl derivative of aminothiazole (I) has been used for the synthesis of azoloazepines -in particular, with the general formula II -which also possess antimicrobial properties [4]. This class of substances also includes corazole and compounds III, which were proposed for the treatment of growth disturbances in children, Parkinson's disease, and schizophrenia [4,5].In this context, it was of interest to study the most effective methods for the synthesis of 2-AT and obtain a series of new derivatives. The synthesis of AT using a method described previously [6], which is based on the selective bromination of ketones in DMF in the presence of urea, followed by the cyclization of intermediate a-bromoketones with thiourea in situ, is sometimes accompanied by resinification that complicates purification of the target products. In continuation of that investigation, we have studied the dependence of the yield and purity of 2-AT on the amount of urea used in the bromination stage.It was found that, using a bromoketone/urea molar ratio of 1 : (3 -3.5), it is possible to reduce the probability of formation of isomeric mono-, di-, and tribromides, which simplifies the isolation of 2-AT, increases the yield, and provides higher purity of the target product. Further increase in the amount of urea does not change the final results (Scheme 1).

Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study

“…The α-chloropropanals were immediately converted into the aminothiazole scaffold ( 15a – f , 16a – g ) by condensation with thiourea . The aminothiazoles were subsequently chloroacetylated to yield 17a – j and 18a – i , followed by a nucleophilic substitution with an aromatic thiol to generate compounds 14a – r , 19a – q , and 20a – d . The synthesis of the halogenated 1-naphthylamines ( 21a – c ), which were needed as starting materials for the synthesis of the halogenated inhibitors ( 14a , 14d , 14f , 14g , and 14i ), is illustrated in Scheme by the example of the chlorinated 1-naphthylamines 21a – b .…”

Synthesis and Spectroscopic Studies of New Schiff Bases

“…The precipitated thiazole was collected and purified by crystallization from hot ethanol. Method B: 2-Amino-4-(2'-bromophenyl)-thiazole was also prepared following the reported procedure [14]. The spectroscopic data of the compound 1a thus prepared were identical to those given above.…”

Strukturbasierte Entwicklung einer Affinitätssonde für Sirtuin 2

“…[19] Zuletzt wurde 8 in einer Cu-katalysierten HuisgenCycloaddition zu 9 und 10 oder zur SirReal-Affinitätssonde (11)umgesetzt. [20] Die Triazole 9 und 10 konnten durch Te stung in einem homogenen fluoreszenzbasierten Sirt2-Aktivitätsassay [21] als neue Sirt2-Hemmstoffe identifiziert werden (Tabelle 1), die mehr als 20-fach potenter sind als ihre Stammverbindung SirReal1 (1).…”