反应详情

To a solution of tert-butyl 1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)-quinolin-2-yl)ethylcarbamate (0.23 g, 0.50 mmol) in DCM (5 mL) was added trifluoroacetic acid (0.97 mL, 12.5 mmol) and the resulting solution was stirred at room temperature for one hour. The solution was concentrated under reduced pressure then diluted with 1-butanol (2.5 mL) followed by the addition of 4-amino-6-chloropyrimidine-5-carbonitrile (0.082 g, 0.53 mmol) and diisopropylethylamine (0.26 mL, 1.51 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (0.082 g, 0.53 mmol). The solution was stirred at 120° C. for 3 h then purification was attempted by silica gel column chromatography eluting with 0-100% (1:10:90 NH4OH:MeOH:DCM) in DCM). The resulting crude solid was repurified by silica gel column chromatography eluting with a gradient of 0-7% MeOH in DCM to afford a mixture of (R) and (S)-4-amino-6-(1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylamino)pyrimidine-5-carbonitrile as a yellow glass: LC-MS (ESI) m/z 477.2 [M+H]+.

1. concentrationThe solution was concentrated under reduced pressure
2. additionthen diluted with 1-butanol (2.5 mL)
3. stirringThe solution was stirred at 120° C. for 3 h
4. custompurification
5. washeluting with 0-100% (1:10:90 NH4OH:MeOH:DCM) in DCM)
6. customThe resulting crude solid was repurified by silica gel column chromatography
7. washeluting with a gradient of 0-7% MeOH in DCM
8. customto afford