反应详情

温度

-78 °C

Under an atmosphere of argon protective gas, (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 (13 mg, 28 μmol) was initially charged in abs. dichloromethane (2 ml). At −78° C., 4-nitrophenyl chloroformate (28.6 mg, 142 μmol, 5 eq.), triethylamine (14.7 mg, 145 μmol, 5.1 eq.) and DMAP (3.5 mg, 28 μmol) were added. After 2 h of stirring at −78° C., the reaction mixture was allowed to thaw initially to −20° C. (2 h) and then to 0° C. (2 h). The mixture was then once more cooled to −78° C., and a 2 M solution of methylamine in THF (102 μl, 7.2 eq.) was added. The mixture was then warmed to −10° C. and stirred overnight. A 2 M solution of methylamine in THF (1 ml) was then added, the reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (Reprosil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (5.9 mg, 43% of theory).

1. customthaw initially to −20° C. (2 h)
2. customto 0° C.
3. custom(2 h)
4. temperatureThe mixture was then once more cooled to −78° C.
5. temperatureThe mixture was then warmed to −10° C.
6. stirringstirred overnight
7. concentrationthe reaction mixture was concentrated under reduced pressure
8. customthe residue was purified by preparative HPLC (Reprosil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
9. customAfter lyophilization, the product was obtained as a solid (5.9 mg, 43% of theory)