Amino-thienopyrimidine Series

Repeat of AT-6-1, with the use of more starting material AT-5 (0.100 g, 0.40 mmol) and less solvent (2 M NH₃ in isopropanol, 8 mL). 

Analysis of the reaction mixture after 18 hours by TLC showed only traces of product, with the majority as starting material. The reaction was restarted, with the use of a freshly prepared sample of ammonia/isopropanol, rather than the solution prepared previously.  

Still only minimal conversion (as assessed by TLC) of starting material after 36 hours. 

The volatiles were removed under reduced pressure and the residue resuspended in isopropanol:ammonia (1:1, 10 mL) and stirred in a sealed tube at 100 C. Analysis by TLC after 3 hours showed more conversion to product (relative intensity of the product spot, with respect to starting material, was greater under these conditions). Reaction mixture left to stir overnight. 

The reaction was stopped and allowed to cool to rt. The volatiles were removed and the residue purified by flash column chromatography (95:4.5:0.5 dichloromethane:methanol:ammonia) to give the product as a yellow solid (0.051 g, 55%). 

HIRAC