반응 #10420

반응 방정식

sodium tert-butoxide

chlorosulfonyl isocyanate

sodium acetate

ethyl 2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinate

→

title compound

수율 18.5%

1-Cyclopropyl-6-fluoro-7-methylsulfanyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione

수율 18.5%

용매

dichloromethane

반응 조건

후처리

1. 1
   workup.WAITto come to room temperature overnight
2. 2
   기타is recooled to −20° C.
3. 3
   workup.STIRRINGAfter stirring for 1 hour
4. 4
   온도without cooling
5. 5
   기타the solvent is removed in vacuo
6. 6
   온도without heating
7. 7
   기타The residue is triturated with a saturated solution of sodium acetate in brine
8. 8
   추출extracted with ethyl acetate (3×75 mL)
9. 9
   건조The combined organic layers are dried (MgSO4)
10. 10
    여과filtered
11. 11
    기타evaporated in vacuo
12. 12
    workup.STIRRINGstirred at room temperature for 36 hours
13. 13
    기타The solvent is removed in vacuo
14. 14
    기타the residue triturated with 100 mL of 0.1 M formic acid
15. 15
    추출extracted with ethyl acetate (3×100 mL)
16. 16
    세척The combined organic layers are washed with water
17. 17
    건조dried (MgSO4)
18. 18
    여과filtered
19. 19
    기타evaporated in vacuo
20. 20
    기타to give a residue which
21. 21
    기타is chromatographed over flash grade silica gel (230–400 mesh)
22. 22
    세척eluting with dichloromethane

실험 절차

A solution of 4.1 g (15.2 mmol) of ethyl 2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinate (Example 34) in 125 mL of dichloromethane is cooled to −20° C. and treated dropwise with 5.24 g (37 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 3 hours and allowed to come to room temperature overnight. The mixture is recooled to −20° C. and treated with 6.8 g (80 mmol) of solid sodium acetate. After stirring for 1 hour without cooling, the solvent is removed in vacuo without heating. The residue is triturated with a saturated solution of sodium acetate in brine and extracted with ethyl acetate (3×75 mL). The combined organic layers are dried (MgSO4), filtered and evaporated in vacuo. The residue is suspended in 100 mL of tetrahydrofuran and treated with 3.6 g (32 mmol) of solid sodium tert-butoxide and stirred at room temperature for 36 hours. The solvent is removed in vacuo, the residue triturated with 100 mL of 0.1 M formic acid and extracted with ethyl acetate (3×100 mL). The combined organic layers are washed with water, dried (MgSO4), filtered and evaporated in vacuo to give a residue which is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane to give 0.75 g of the title compound, mp 220–222° C.

출처