反应详情

温度

25 °C

3.2 g 2-Chloro-4,6-dimethoxy-1,3,5-traizine (CDMT) was charged to a mixture of 2.8 g 2-chloro-4-(methylsulfonyl)benzoic acid (Formula F) in 80 mL methylene dichloride (MDC) under nitrogen atmosphere at 25-30° C. and stirred for about 20 mins 4.9 g N-methyl morpholine (NMM) was added to the reaction mixture over period of about 15 mins maintaining temperature of 20-30° C. Reaction mixture was maintained under stirring at this temperature for about 3 hrs. 2 g 4-chloro-3-(pyridin-2-yl)benzenamine (Formula E) was then added to the reaction mixture and stirring was done for additional 3 hrs at same temperature. Then the temperature of reaction mixture was raised to 35-40° C. and stirring was done, intermittently checking reaction progress by TLC. On completion of the reaction, reaction mixture was cooled to 20-30° C. and quenched with 40 mL water. Organic layer was separated and the aqueous layer was washed with 20 mL MDC. MDC organic layer was collected and washed twice with 40 mL saturated sodium bicarbonate solution followed by a water washing (40 mL). Organic layer was dried over sodium sulphate and solvent was distilled off under vacuum at 35-45° C. to obtain a residue. To this residue, 30 mL Iso-propyl alcohol (IPA) was added and reaction temperature was raised to 60-70° C., wherein stirring was performed for about 30 mins followed by slow cooling to 20-30° C. Reaction was maintained for about 1 hr at same temperature under stirring. The precipitated product was filtered on Buchner funnel, washed with 10 mL IPA and dried at 40-45° C. under vacuum to get 2.5 g 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide (I) having HPLC area purity of 99.3%.

1. additionwas added to the reaction mixture over period of about 15 mins
2. customReaction mixture
3. temperaturewas maintained
4. stirringstirring
5. waitwas done for additional 3 hrs at same temperature
6. customThen the temperature of reaction mixture
7. temperaturewas raised to 35-40° C.
8. stirringstirring
9. customreaction progress by TLC
10. customOn completion of the reaction, reaction mixture
11. temperaturewas cooled to 20-30° C.
12. customquenched with 40 mL water
13. customOrganic layer was separated
14. washthe aqueous layer was washed with 20 mL MDC
15. customMDC organic layer was collected
16. washwashed twice with 40 mL saturated sodium bicarbonate solution
17. dry with materialOrganic layer was dried over sodium sulphate and solvent
18. distillationwas distilled off under vacuum at 35-45° C.
19. customto obtain a residue
20. customreaction temperature
21. temperaturewas raised to 60-70° C.
22. stirringwherein stirring
23. waitwas performed for about 30 mins
24. temperatureby slow cooling to 20-30° C
25. customReaction
26. temperaturewas maintained for about 1 hr at same temperature
27. stirringunder stirring
28. filtrationThe precipitated product was filtered on Buchner funnel
29. washwashed with 10 mL IPA
30. customdried at 40-45° C. under vacuum