反应详情

温度

60 °C

To a slurry of azetidine hydrochloride (126 mg, 1.35 mmol) in THF (1.0 ml) was added a scoop of Aberlite-IRA-93 ion exchange resin, which was shaken 3 minutes to give a solution, dried with anhydrous Na2SO4 and filtered to remove resin. Then methanesulfonic acid 2-[3-(2-oxo-1,2-dihydro-indol-3-ylidene)-1,3-dihydro-isobenzofuran-1-yl]-ethyl ester (50.0 mg, 0.135 mmol) was added to the amine solution and heated at 60° C. for 18 hours (no reaction had occurred). After standing at room temperature for 2 days, to the mixture were added dioxane (0.3 ml), azetidine hydrochloride (63 mg, 0.675 mmol), and triethylamine (132 μl, 0.945 mmol). The resulting mixture was stirred at room temperature for 3 days, and heated at 60° C. for 24 hours. The reaction was partitioned between water and EtOAc. The EtOAc layer was extracted with 4% HCl aqueous solution, and then the aqueous layer was basified with saturated NaHCO3 aqueous solution. The basified aqueous layer was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and rotary evaporated to give a film. The film was chromatographed (2.5% to 5% MeOH/CHCl3 gradient) to provide 3-[3-(2-azetidin-1-yl-ethyl)-3H-isobenzofuran-1-ylidene]-1,3-dihydro-indol-2-one as a yellow film (8.7 mg, 19%).

1. customto give a solution
2. dry with materialdried with anhydrous Na2SO4
3. filtrationfiltered
4. customto remove resin
5. waitAfter standing at room temperature for 2 days, to the mixture
6. stirringThe resulting mixture was stirred at room temperature for 3 days
7. temperatureheated at 60° C. for 24 hours
8. customThe reaction was partitioned between water and EtOAc
9. extractionThe EtOAc layer was extracted with 4% HCl aqueous solution
10. extractionThe basified aqueous layer was extracted with EtOAc
11. washThe organic layer was washed with brine
12. dry with materialdried over anhydrous Na2SO4
13. customrotary evaporated
14. customto give a film
15. customThe film was chromatographed (2.5% to 5% MeOH/CHCl3 gradient)