N-acetylchloroacetamide in the synthesis of functionally-substituted pyrido[3′,2′∶4,5]-thieno[3,2-d]pyrimidin-4(3H)-ones

Abstract

Functionally-substituted pyrido [3',2':4,5]thieno [3,2-d]pyrimidinones hold interest as compounds, which may possess a broad range of biological activity. The known methods for the preparation of such compounds involve the reaction of 3-amino-2-carbamoylthienopyridines with acetonitrile in the presence of HC1 in dioxane [1], acylation of 3-amino-2-ethoxycarbonylthienopyridines by acetic anhydride followed by treatment with ammonia [2], reaction of 3-amino-2-carbamoylthienopyridines with acetic anhydride [3][4][5] or triethyl orthoformate [6], and also acylation of 3-aminothieno-2-pyridinecarboxylic acid with subsequent reaction of the pyridothienooxazinone formed with ammonia [6]. These multistep procedures require vigorous conditions and do not always provide high yields. Furthermore, compounds with fused carbocyclic fragments containing an odd number of carbon atoms cannot be obtained using these methods.We propose a new convenient method for the regioselective synthesis of functionally-substituted pyrido-[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-ones starting from N-acetylchloroacetamide (I) and 3-cyano-2(1H)-pyridinethiones (IIa-IIf), which avoids the indicated drawbacks.N-Acetylchloroacetamide I may be obtained by the acylation of chloroacetamide by acetic anhydride in the presence of acetyl chloride [7], reaction of chloroacetonitrile with glacial acetic acid [8], reaction of acetamide with chloroacetamide in the presence of HC1 [8], and also the reaction of acetamide with chloroacetyl chloride [9].

Thienopyridines: synthesis, properties, and biological activity

“…The starting compounds 87 can be generated in situ from 3 cyanopyridine 2(1H ) thiones 7 (Scheme 26). 88 Analogously, pyrido[3´,2´:4,5]thieno[3,2 d]pyrimi dine 90 is derived from N cyanoamide 89 in moderate yield under mild conditions (Scheme 27). 81a The treat ment of pyridinethiones 7 (R 1 , R 3 = Ar, R 2 = H) with N (ethoxycarbonyl)chloroacetamide 91 provides a con venient one pot method for the synthesis of tricyclic thienoazines 92.…”

Heterocyclic synthesis with 4-hydrazinopyridothienopyrimidines: Synthesis of pyridothienotriazolopyrimidines and heterocyclylpyridothienopyrimidines with biological interest

“…This constitutes a simple and easy one pot reactions leading to functionally substituted tricyclic products, which otherwise are difficult to access. A similar reaction has been reported previously [27]. Compounds 5a,b were refluxed in an excess of phosphorus oxychloride to give the respective 4-chloropyrimidines 6a,b which, upon reaction with hydrazine hydrate, produced the title precursors 7a,b (Scheme 1).…”