反应详情

温度

0 °C

A mixture of 1-methyl-1H-pyrazole-4-carboxylic acid (22 mg, 0.17 mmol) in dichloromethane (2.0 mL) at 25° C. was treated with triphenylphosphine (54 mg, 0.21 mmol). This mixture was cooled to 0° C. and then treated with N-chlorosuccinimide (28 mg, 0.21 mmol). This mixture was stirred at 0° C. for 30 min and then was warmed to 25° C. At this time, the reaction was treated with 3-cyclopropylmethyl-1-(2-fluoro-benzyl)-8-(4-methylamino-benzyl)-3,7-dihydro-purine-2,6-dione (150 mg, 0.34 mmol). The reaction was then stirred at 25° C. for 2 days. At this time, the reaction was diluted with dichloromethane and then was washed with a saturated aqueous sodium bicarbonate solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3:97 methanol/dichloromethane) afforded 1-methyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (87 mg, 92.8%) as an off-white solid: LR-MS for C29H28FN7O3 (M+H)+ at m/z=542.

1. temperaturewas warmed to 25° C
2. stirringThe reaction was then stirred at 25° C. for 2 days
3. washwas washed with a saturated aqueous sodium bicarbonate solution
4. dry with materialThe organics were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo