D-Ribofuranose, 1,2,3,5-tetraacetate → Thiazolo[4,5-d]pyrimidin-2-one
Reaction equation
Cl[C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.C(OC1O[C@H](COC(=O)C)[C@@H](OC(=O)C)[C@H]1OC(=O)C)(=O)C>>[S:10]1[C:5]2[CH:4]=[N:3][CH:2]=[N:7][C:6]=2[NH:8][C:9]1=[O:11]Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-c26ac7d6807847f9b0e97f06c43f2732
- Source dataset
- uspto-grants-1991_08
- Patent number
- US05041426
Reaction notes
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