D-Ribofuranose, 1,2,3,5-tetraacetate → Thiazolo[4,5-d]pyrimidin-2-one

Participants

Reaction Steps

In an effort to study the thiazolo[4,5-d]pyrimidine ring system with respect to the order of nucleophilic substitution at the 2,5, and 7 positions and possibly use this information to synthesize the adenosine analog, chlorination of the readily available 2-chlorothiazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione (21) using refluxing POCl3 and N,N-dimethylaniline (Scheme IV) was effected. The desired 2,5,7-trichlorothiazolo[4,5,-d]pyrimidine (22) was obtained along with a small amount of 5,7-dichloro-2-(N-methylanilino)thiazolo[4,5-d]pyrimidine (23). The trichloro compound, 22, was carefully hydrolyzed in 1N NaOH at 60° C. in order to obtain the mono-oxo derivative, 5,7-dichlorothiazolo[4,5-d]pyrimidin-2(3H)-one (24), the structure of which was verified by single crystal X-ray analysis. Reaction of 24 with 1,2,3,5-tetra-O-acetyl-D-ribofuranose (25) under fusion glycosylation conditions produced 5,7-dichloro-3-2,3,5-tri-O-acetyl-β-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-one (26). Attempts to use 26 for further modification to obtain the adenosine analog were unsuccessful due to the labile nature of the thiazole ring toward nucleophilic ring-opening.

Provenance & Evidence