反应详情

After the atmosphere in the reaction vessel had been replaced with nitrogen, the tetrahydrofuran solution containing Carbonic acid 2-(3-{1-(4-cyanophenylamino)-2-[ethoxycarbonylimino]-2-methylsulfanylethyl]-2-fluoro-5-methoxyphenoxy)ethyl ester ethyl ester obtained in Example 64 was added, rinsing in with tetrahydrofuran (1250 mL) and stirred. Thereafter, pyrimidin-2-yl-hydrazine (275 g, 2.497 mol) was added portionwise at a bath temperature of 15° C., rinsing in with tetrahydrofuran (1000 mL), and the mixture was stirred at a bath temperature of 22° C. for 14 hours. Pyrimidin-2-yl-hydrazine (8.2 g, 0.074 mol) was additionally added, rinsing in with tetrahydrofuran (30 mL), and stirring was continued for one hour. Thereafter, the bath temperature was set at 15° C., 1,8-diazabicyclo[5.4.0]undec-7-ene (304 g, 1.999 mol) was added dropwise to the mixture, rinsing in with tetrahydrofuran (50 mL), and then the bath temperature was set at 22° C. and the mixture was stirred for 2.5 hours. Thereafter, the bath temperature was set at 15° C., and ethyl acetate (7504 mL) and 1 N hydrochloric acid (7504 mL) were added to the reaction solution. Then, the bath temperature was set at 22° C., the organic layer was collected, and the aqueous layer was further extracted with ethyl acetate (3752 mL). All the organic layers were combined, the organic layer was washed with 10% aqueous sodium chloride solution (7504 g) twice, and concentrated under reduced pressure. The residue obtained was subjected to azeotropic distillation three times with methanol (1250 mL of methanol was used, each time). To the residue obtained, tetrahydrofuran (375 mL) and methanol (475 mL) were added to obtain the suspension of the captioned compound.

1. additionwas added
2. washrinsing in with tetrahydrofuran (1250 mL)
3. washrinsing in with tetrahydrofuran (1000 mL)
4. stirringthe mixture was stirred at a bath temperature of 22° C. for 14 hours
5. washrinsing in with tetrahydrofuran (30 mL)
6. stirringstirring
7. customwas set at 15° C.
8. washrinsing in with tetrahydrofuran (50 mL)
9. customwas set at 22° C.
10. stirringthe mixture was stirred for 2.5 hours
11. customwas set at 15° C.
12. additionethyl acetate (7504 mL) and 1 N hydrochloric acid (7504 mL) were added to the reaction solution
13. customwas set at 22° C.
14. customthe organic layer was collected
15. extractionthe aqueous layer was further extracted with ethyl acetate (3752 mL)
16. washthe organic layer was washed with 10% aqueous sodium chloride solution (7504 g) twice
17. concentrationconcentrated under reduced pressure
18. customThe residue obtained
19. distillationwas subjected to azeotropic distillation three times with methanol (1250 mL of methanol
20. customTo the residue obtained
21. customto obtain
22. additionthe suspension of the captioned compound