반응 #2146755

반응 방정식

(2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol

(2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol

triethylamine

DMF

trimethylsilylacetylene

→

title compound

(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

용매

THF

ammonia

methanol

반응 조건

후처리

1. 1
   기타To a dried
2. 2
   기타The solvent is removed in vacuo
3. 3
   기타the residue obtained
4. 4
   기타The resulting reaction mixture
5. 5
   workup.STIRRINGto stir at room temperature for one hour
6. 6
   기타The solvent is removed in vacuo
7. 7
   기타The crude residue obtained

실험 절차

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.

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