Triethylamine → 5-chloro-1,3-dimethyl-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

Temperatur

0 °C

A mixture of 5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylic acid (40 mg, 0.231 mmol) in dichloromethane (2.0 mL) at 25° C. was treated with triphenylphosphine (72 mg, 0.28 mmol). The reaction was cooled to 0° C. and then was treated with N-chlorosuccinimide (37 mg, 0.28 mmol). This mixture was stirred at 0° C. for 5 min and then was warmed to 25° C. for 15 min. 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 (100 mg, 0.23 mmol) and triethylamine (0.04 mL, 0.28 mmol). This mixture was stirred at 25° C. for 24 h. At this time, the reaction was diluted with dichloromethane (50 mL) and then was washed with a IN aqueous hydrochloric acid solution (1×50 mL) and a saturated aqueous sodium bicarbonate solution (1×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1:99 methanol/dichloromethane) afforded 5-chloro-1,3-dimethyl-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 (54 mg, 48%) as a white solid: LR-MS for C30H29ClFN7O3 (M+H)+ at m/z=590.

1. temperaturewas warmed to 25° C. for 15 min
2. stirringThis mixture was stirred at 25° C. for 24 h
3. washwas washed with a IN aqueous hydrochloric acid solution (1×50 mL)
4. dry with materialThe organics were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD-Eintrag

ord-99e695ae274644d2ad7e3b335336a555

Quelldatensatz

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07135475B2