反应详情

温度

40 °C

To a slurry of di-tert-butyl {6-[8-({4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl}amino)imidazo[1,2-a]pyrazin-6-yl]pyrazin-2-yl}imidodicarbonate (225 g, 0.35 mol, 1 mol eq.) in water (12 parts) was added a solution of sulfuric acid (3.1 parts, 6.99 mol, 20 mol eq.) in water (5 parts). The reaction was heated to ca. 40° C. and stirred at this temperature for ca. 4 h at which point the reaction is deemed complete. The reaction mixture was cooled to ca. 22° C., acetone (3 parts) was charged and a solution of sodium carbonate (4.1 parts, 8.75 mol, 25.0 mol eq.) in water (15 parts) was added. The resulting slurry was filtered and the wet cake was washed with water in portions (4×1 parts), then with tert-butyl methyl ether (4 parts). The wet cake (Example 2 free base) was dried at ca. 60° C. To the slurry of dry Example 2 free base in 2-propanol (2.3 parts) was added a solution of succinic acid (Based on the isolated Example 2 free base: 0.43 parts, 1.6 mol eq.) in 2-propanol (15 parts). The resulting slurry was heated to ca. 40° C. and stirred at this temperature for ca. 2 h and then cooled to ca. 22° C., followed by a stir period of ca. 16 h. The slurry was filtered at ca. 22° C. and the wet cake was washed with 2-propanol (5 parts) and dried at ca. 60° C. to afford the product.

1. temperatureThe reaction mixture was cooled to ca. 22° C.
2. filtrationThe resulting slurry was filtered
3. washthe wet cake was washed with water in portions (4×1 parts)
4. customThe wet cake (Example 2 free base) was dried at ca. 60° C
5. additionTo the slurry of dry Example 2 free base in 2-propanol (2.3 parts) was added a solution of succinic acid (
6. temperatureThe resulting slurry was heated to ca. 40° C.
7. stirringstirred at this temperature for ca. 2 h
8. temperaturecooled to ca. 22° C.
9. waitfollowed by a stir period of ca. 16 h
10. filtrationThe slurry was filtered at ca. 22° C.
11. washthe wet cake was washed with 2-propanol (5 parts)
12. customdried at ca. 60° C.
13. customto afford the product