反应详情

温度

1 °C

(7R)-2-Amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (400 mg, 1.0 mmol; Example 7, free base) was dissolved in a mixture of acetic acid, conc. hydrochloric acid and water (2:1:1, 10 ml) at RT. At −10° C., a solution of sodium nitrite (72 mg, 1.0 mmol, 1.1 eq.) in water (1.1 ml) was slowly added dropwise to the reaction mixture. The mixture was allowed to warm to 0-2° C. and then cooled once more to −10° C. This solution was added to a solution of glacial acetic acid (11 ml) whose temperature had been adjusted to −10° C. beforehand and which had been saturated with sulfur dioxide gas and to which copper(I) chloride (18.8 mg, 0.019 mmol, 0.2 eq.) had been added. For a short while, there was a vigorous reaction. The mixture was stirred at −10° C. for 1 h, then warmed to 15° C. and stirred for another 1 h. The reaction solution was then once more cooled to 0° C. The product was precipitated by dropwise addition of this reaction solution to stirred ice-water (60 ml). The beige precipitate was filtered off, taken up in ethyl acetate, washed with saturated sodium chloride solution and then dried over sodium sulfate. After filtration, the mixture was concentrated under reduced pressure and the residue was dried under high vacuum. The product was obtained as a solid (415 mg, 63% pure, 55% of theory).

1. temperaturecooled once more to −10° C
2. customhad been adjusted to −10° C.
3. additionhad been added
4. customa vigorous reaction
5. temperaturewarmed to 15° C.
6. stirringstirred for another 1 h
7. temperatureThe reaction solution was then once more cooled to 0° C
8. customThe product was precipitated by dropwise addition of this reaction solution
9. stirringto stirred ice-water (60 ml)
10. filtrationThe beige precipitate was filtered off
11. washwashed with saturated sodium chloride solution
12. dry with materialdried over sodium sulfate
13. filtrationAfter filtration
14. concentrationthe mixture was concentrated under reduced pressure
15. customthe residue was dried under high vacuum
16. customThe product was obtained as a solid (415 mg, 63% pure, 55% of theory)