N-Iodosuccinimide → 6-Chloro-7-iodo-7-deazapurine

Participants

Reaction Steps

The tricyclic nucleoside 6.7 was synthesized starting from 4-chloro-1H-pyrrolo[2,3-d]pyrimidine 2.1. The nucleobase 2.1 was treated with N-iodosuccinimide in THF at room temperature for 4 hr to provide 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine 6.1. Then 6.1 was converted to the corresponding sodium salt with sodium hydride in acetonitrile and reacted with bromo-sugar 2.4 ((i)Helv. Chim. Acta. 1995, 78, 486; (ii) WO 02/057287, 2002), to give nucleoside 6.2. which was directly converted to 4-amino-5-iodo-7-[3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine 6.3. A Stille coupling reaction between nucleoside 6.3 and Z-3-tributylstannylacrylate provided compound 6.4. The cyclization of compound 6.4 was accomplished by heating in DBU/dioxane overnight to afford the protected tricyclic nucleoside 6.5, which was then treated with boron trichloride in CH2Cl2 to produce nucleoside 6.6.

Provenance & Evidence