反应详情

温度

0 °C

3,5-Difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile (0.105 g, 0.21 mmol) is dissolved in DMF (5 mL) and cooled down to 0° C. To this is added Et3N (0.043 mL, 0.31 mmol) and methanesulfonyl chloride (0.019 mL, 0.25 mmol). After 2 h, LCMS showed the presence of the intermediate mesylate [MS (ESI) m/z 584.3 (M+H)]. The solution is evaporated to dryness and dissolved in DMF (5 mL), to which is added K2CO3 (0.086 g, 0.62 mmol) and NaI (0.093 g, 0.62 mmol) and the mixture is heated to 90° C. for 0.5 h. The solution is then evaporated, dissolved in MeCN and filtered. The crude residue is purified via flash column chromatography (MeOH/DCM 1:99→MeOH/DCM 1:9) to give 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3,5-difluorobenzonitrile. MS (ESI) m/z 246.2 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.72-2.85 (m, 1H), 2.93-3.05 (m, 1H), 3.08-3.21 (m, 2H), 5.75 (app t, J=7.2 Hz, 1H), 6.79 (s, 1H), 7.18-7.41 (m, 3H).

1. customThe solution is evaporated to dryness
2. dissolutiondissolved in DMF (5 mL), to which
3. temperaturethe mixture is heated to 90° C. for 0.5 h
4. customThe solution is then evaporated
5. dissolutiondissolved in MeCN
6. filtrationfiltered
7. customThe crude residue is purified via flash column chromatography (MeOH/DCM 1:99→MeOH/DCM 1:9)