Dimethylformamide → HCID 24962647, compound

Participants

Reaction Steps

Alternatively, the title compound and the compounds of Examples 9 and 10 are prepared from (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol (Example 7). To a dried and precooled 25 ml round-bottomed flask are added (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol (0.060 g, 0.144 mmol), copper(I) iodide (0.006 g, 0.028 mmol), tetrakis(triphenylphosphine)palladium(0) (0.016 g, 0.014 mmol) dissolved in anhydrous THF (1.0 ml) and anhydrous DMF (0.5 ml), triethylamine (0.04 ml, 0.288 mmol), trimethylsilylacetylene (0.024 ml, 0.173 mmol). The reaction mixture is stirred at 0° C. to room temperature under argon for 30 mins. The solvent is removed in vacuo, and the residue obtained is dissolved in methanol (0.60 ml) and 30% ammonia solution (0.60 ml). The resulting reaction mixture is allowed to stir at room temperature for one hour. The solvent is removed in vacuo. The crude residue obtained is purified by reverse phase preparative HPLC on Atlantis C18 column (250×20 mm) in gradient from 5 to 95% of acetonitrile in water. Fractions containing the desired products are isolated, evaporated and lyophilized from water to give (2R,3R,4R,5R)-2-(4-amino-5-ethynyl-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 8), (2R,3R,4R,5R)-2-(4-amino-5-ethynyl-pyrrolo[2,3-d]pyrimidin-7-yl)-3-buta-1,3-diynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 9), and (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-buta-1,3-diynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 10) as white solid.

Provenance & Evidence