反应详情

温度

110 °C

2-Phenylacetamide (149 mg) was dissolved in 1,2-dichloroethane (10 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.175 ml) was added thereto, followed by stirring at 110° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (3.4 ml) under a nitrogen atmosphere. 3-[4-(4-Aminophenoxy)pyridin-2-yl]-1,1-dimethylurea (100 mg) was then added thereto, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3). Fractions containing a crude product were concentrated under a reduced pressure to give a residue, which was then partitioned between ethyl acetate and 1N hydrochloric acid. To the aqueous layer was added a 1 N aqueous solution of sodium hydroxide to make it alkaline, which was then extracted with ethyl acetate. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product, which was then partitioned between ethyl acetate and 1N hydrochloric acid again. To the aqueous layer was added a 1 N aqueous solution of sodium hydroxide to make it alkaline, which was then extracted with ethyl acetate. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product, which was then partitioned between ethyl acetate and 1N hydrochloric acid again. To the aqueous layer was added a 1 N aqueous solution of sodium hydroxide to make it alkaline, which was then extracted with ethyl acetate. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product, which was then partitioned between ethyl acetate and 1N hydrochloric acid. To the aqueous layer was added a 1 N aqueous solution of sodium hydroxide to make it alkaline, which was then extracted with ethyl acetate. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which were added a small amount of ethyl acetate and a small amount of hexane to precipitate crystals. The crystals were filtered off and dried under aeration to provide the titled compound (8.1 mg, 5.1%) as pale yellow crystals.

1. concentrationThe reaction mixture was concentrated under a reduced pressure
2. customto give a residue, which
3. stirringby stirring for 30 min
4. customThe reaction mixture was partitioned between ethyl acetate and water
5. washThe organic layer was washed with water and brine in this order
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was evaporated
8. customto give a residue, which
9. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3)
10. additionFractions containing a crude product
11. concentrationwere concentrated under a reduced pressure
12. customto give a residue, which
13. customwas then partitioned between ethyl acetate and 1N hydrochloric acid
14. additionTo the aqueous layer was added a 1 N aqueous solution of sodium hydroxide
15. extractionwas then extracted with ethyl acetate
16. washThe organic layer was washed with water and brine in this order
17. dry with materialdried over anhydrous sodium sulfate
18. customThe solvent was evaporated
19. customto give a crude product, which
20. customwas then partitioned between ethyl acetate and 1N hydrochloric acid again
21. additionTo the aqueous layer was added a 1 N aqueous solution of sodium hydroxide
22. extractionwas then extracted with ethyl acetate
23. washThe organic layer was washed with water and brine in this order
24. dry with materialdried over anhydrous sodium sulfate
25. customThe solvent was evaporated
26. customto give a crude product, which
27. customwas then partitioned between ethyl acetate and 1N hydrochloric acid again
28. additionTo the aqueous layer was added a 1 N aqueous solution of sodium hydroxide
29. extractionwas then extracted with ethyl acetate
30. washThe organic layer was washed with water and brine in this order
31. dry with materialdried over anhydrous sodium sulfate
32. customThe solvent was evaporated
33. customto give a crude product, which
34. customwas then partitioned between ethyl acetate and 1N hydrochloric acid
35. additionTo the aqueous layer was added a 1 N aqueous solution of sodium hydroxide
36. extractionwas then extracted with ethyl acetate
37. washThe organic layer was washed with water and brine in this order
38. dry with materialdried over anhydrous sodium sulfate
39. customThe solvent was evaporated
40. customto give a residue
41. customa small amount of hexane to precipitate crystals
42. filtrationThe crystals were filtered off
43. customdried under aeration