Synthesis and alkylation of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-ones

Abstract

The one-step method for preparation of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-ones by interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with ortho-pnenylediamines using 1,1'-carbonyldiimidazole as a coupling-reagent has been developed. The procedure proposed allows to obtain easily the target products using common reagents and solvents; and it also requires the simple isolation methods. The selectivity of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one interaction with benzyl chlorides in DMF-К 2 СО 3 conditions has been studied using the NOESY spectroscopic method and alternative synthetic approaches; it has been determined that the reaction occurs at position 3 of the thieno[2,3-d] pyrimidine system. The study of the antimicrobial activity by the agar diffusion method for the compounds obtained has shown that 6-(1H-benzimidazol-2-yl)-3-benzyl-5-methylthieno[2,3-d]pyrimidin-4(3H)-ones reveal the antimicrobial activity against the strains of Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa; while the compound with unsubstituted position 3 appeared to be inactive against these strains of microorganisms. However, this compound exhibited the higher inhibitory activity against the Candida albicans fungi.

The synthesis, antimicrobial activity and docking studies of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin- 4(3H)-ones with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents

“…Taking into account the positive results of our previous research on the regioselectivity of the alkylation of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one with benzyl chlorides [3], as well as some successful experience of the transfer of the method developed for benzyl chlorides to chloroacetamides for the similar systems with the fragment of 5-methylthieno [2,3-d]pyrimidin-4(3H)-one [4] we decided to do the same for benzimidazole containing derivatives. The starting compound 1 obtained according to the method previously reported [3] was treated with either N-arylchloroacetamides or 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in the DMF media using the equimolar amount of potassium carbonate to promote the reaction (Scheme).…”

“…Derivatives of 6-(1H-benzimidazol-2-yl)thieno- [2,3-d]pyrimidines attract attention of researchers as promising biologically active compounds. Earlier different preparation methods for these compounds were reported [1 -3], and the selectivity of their alkylation with benzyl chlorides was studied [3]. The works published in recent years has also shown the positive impact of the acetamide or isoxadiazole substituent in position 3 of thieno [2,3-d]pyrimidine on the antimicrobial activity [4,5].…”

Synthesis and the antimicrobial activity of 1-alkyl-5-methyl-3-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones

“…The authors of the article [3] also proposed application of the one-pot method where the corresponding hydrazide reacts with thieno[2,3-d]pyrimidin-6-carboxylic acid right in the POCl 3 media. Recently we have reported the approach using generated in situ imidazolide of thieno[2,3-d]pyrimidin-6-carboxylic acid for the reaction with benzohydrazide suitable for preparation of the product, which after cyclization in phosphorous oxychloride allows forming the 1,3,4-oxadiazole cycle in position 6 of thieno[2,3-d]pyrimidine [4]. Our previous data also reported about some derivatives of thieno [2,3-d]pyrimidine ranges modified at position 6 with azole heterocyles as the compounds with the promising antimicrobial activity [2,4,5,6].…”