反应详情

温度

-10 °C

Under argon, (4R)-4-(2-amino-4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (3.0 g, 7.55 mmol) was initially charged in a 2:1:1 mixture of acetic acid/conc. hydrochloric acid/water (50 ml in total) at −10° C. A solution of sodium nitrite (547 mg, 7.93 mmol) in water (6 ml) was added, and the mixture was stirred at −10° C. for 15 min. This solution was then added to a suspension, pre-cooled to −10° C. and saturated with sulfur dioxide, of copper(I) chloride (75 mg, 755 μmol; 0.1 eq.) in glacial acetic acid (60 ml). The reaction was stirred at −10° C. (internal temperature) for 60 min and then slowly, over a period of 3 h, warmed to +15° C. (reaction monitored by HPLC and LC-MS). The reaction mixture was then once more cooled to 0° C., and then pipetted into about 300 ml of ice-cold water. The aqueous phase was extracted repeatedly with MTBE. The combined organic phases were washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound was obtained as a solid (1.67 g, 73% pure according to LC-MS, 32% of theory) and used without further purification for subsequent reactions.

1. customat −10° C
2. additionThis solution was then added to a suspension
3. stirringThe reaction was stirred at −10° C. (internal temperature) for 60 min
4. waitslowly, over a period of 3 h
5. temperaturewarmed to +15° C.
6. custom(reaction monitored by HPLC and LC-MS)
7. temperatureThe reaction mixture was then once more cooled to 0° C.
8. extractionThe aqueous phase was extracted repeatedly with MTBE
9. washThe combined organic phases were washed twice with saturated sodium chloride solution
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure