反应详情

温度

0 °C

To a solution of 2-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-amine (842 mg) in H2O (20 mL), MeOH (1 mL) and conc. H2SO4 (3 mL) was added aqueous NaNO2 (344 mg) solution drop-wise at 0° C. The mixture was stirred at 0° C. for 15 min and then stirred at reflux temperature for 1 h. The mixture was cooled to room temperature and the pH neutralized with aqueous NaHCO3 solution. It was extracted with DCM (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in-vacuo. The residue was then purified by silica gel chromatography eluted with MeOH:DCM=1:60 and then by Prep-HPLC to afford crude desired product LC-MS: m/e=374 [M+1]+ containing an impurity that was removed by the two-step sequence described below.

1. stirringstirred
2. temperatureat reflux temperature for 1 h
3. temperatureThe mixture was cooled to room temperature
4. extractionIt was extracted with DCM (100 mL×3)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in-vacuo
9. customThe residue was then purified by silica gel chromatography
10. washeluted with MeOH