Synthesis of some new thieno[3,4‐ d ]pyrimidines and their C ‐nucleosides

The synthesis of several new thieno[3,4‐ d ]pyrimidine C ‐nucleosides 5‐8 is described. The known 5‐ribosyl‐ated methyl 4‐(formylamino)thiophene‐3‐carboxylate key intermediate 20 was obtained as a mixture of anomers in significantly improved yield by condensation of the sugar 15 with methyl 4‐(formylamino)thio‐phene‐3‐carboxylate 19 in nitromethane at 60° in the presence of stannic chloride. Attempts to prepare the C‐7 ribosylated compound 21 β by direct condensation of the bicyclic base 10 with 15 gave instead the N‐1 ribosylated nucleoside 16 . The synthesis of the corresponding and previously unknown thieno[3,4‐ d ]pyrimi‐dine bases 12 and 13 is described along with stability studies on the 4‐methylthio derivative 12 . Preliminary biological studies indicate that adenosine analogue 7 is a potent growth inhibitor of several mammalian tumor cell lines.