SYNTHESIS OF THE 6 ISOMERIC THIENO[C]-FUSED 1,5-NAPHYTHYRIDINES AND 1,6-NAPHTHYRIDINES

Through the use of Pd(0)-catalyzed coupling between 2- and 4-formyl-3-thiopheneboronic acids and 3-amino-2-bromopyridine and 4-acetamido-3-bromopyridine, convenient one-pot procedures for the preparation of thieno[2,3-c]-1,5-naphthyridine, thieno[3,4-c]-1,5-naphthyridine, thieno[2,3-c]-1,6-naphthyridine, and thieno[3,4-c]-1,6-naphthyridine have been developed. In order to obtain thieno[3,2-c]-1,6-naphthyridine 2-(tributylstannyl)-3-thiophene aldehyde had to be used, since the organometallic partner in the coupling reaction, 3-formyl-2-thiopheneboronic acid, is too easily deboronated. The effect of silver(I) oxide and thallium(I) carbonate on the coupling was studied. H-1 and C-13 NMR spectra of the six isomeric thieno[c]-fused 1,5- and 1,6-naphthyridines are discussed.