Amide acetals in the synthesis of pyridothienopyrimidines

作者：Medvedeva M I; Tugusheva N Z; Alekseeva L M; Chernyshev V V; Avramenko G V; Granik V G^*

来源：Russian Chemical Bulletin, 2010, 59(10): 1946-1958.

DOI：10.1007/s11172-010-0338-2

• 4-arylamino-2-chloropyridine-3-carbonitriles
• methyl 3-amino-4-arylaminothieno[2,3-b]pyridine-2-carboxylates
• amide acetals
• methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2- carboxylates
• pyridothienopyrimidines
• 5H-1-thia-3,5,8-triazaacenaphthenes
• 3H-1-thia-3,5,8-triazaacenaphthylenes
• the Thorpe-Ziegler reaction
• X-ray diffraction

Methyl 3-amino-4-arylaminothieno[2,3-b]pyridine-2-carboxylates containing various substituents in the benzene ring were synthesized by the Thorpe-Ziegler reaction of 4-arylamino-2-chloropyridine-3-carbonitriles with methyl thioglycolates. The influence of the substituent in the benzene ring, acetal structure, the solvent and the process temperature on the reactions of obtained compounds with amide acetals was studied. It was established that reactions with dimethylacetamide dimethylacetal in toluene smoothly results in amidine derivatives, viz., methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates, regardless of the substituent in the benzene ring. Analogous reaction of p-fluoroderivative with dimethylacetamide dimethylacetal in refluxing anhydrous ethanol leads to intramolecular cyclocondensation to produce substituted pyridothienopyrimidines, viz., 5H-1-thia-3,5,8-triazaacenaphthenes, in good yields. Amidine derivatives were the major products in the case of the coupling of aminothienopyridines with dimethylformamide dimethylacetal under the same conditions. A new approach to the synthesis of substituted pyridothienopyrimidines, viz., 3H-1-thia-3,5,8-triazaacenaphthylenes, based on the prolonged heating of methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates in the excess of acetic anhydride was elaborated. Putative mechanisms of the processes concerned are given.

• 出版日期2010-10
• 单位北京化工大学