تفاعل #41675

معادلة التفاعل

sodium bicarbonate

sodium bicarbonate

triethylamine

methanesulfonyl chloride

N-(4-(4-((t-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide

sodium bicarbonate

→

N-(4-(1-acetyl-3-fluoropyrrolidin-2-yl)-3-fluorophenyl)pyridin-2-carboxamide

المذيبات

Water

chloroform

water

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction liquid
2. 2
   استخلاصextracted with chloroform
3. 3
   تجفيفdried with anhydrous sodium sulfate
4. 4
   أخرىThe solvent was evaporated away under reduced pressure, and 22 mg of sodium azide
5. 5
   workup.ADDITIONwas added to a dimethylformamide (4 ml) solution of the resulting residue
6. 6
   أخرىthe reaction liquid
7. 7
   workup.STIRRINGwas stirred at 40° C. for 2 hours
8. 8
   أخرىThe reaction liquid
9. 9
   درجة الحرارةwas cooled
10. 10
    استخلاصextracted with ethyl acetate
11. 11
    تجفيفdried with anhydrous sodium sulfate
12. 12
    أخرىThe solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution)
13. 13
    workup.ADDITIONwas added to a tetrahydrofuran (4 ml) solution of the resulting residue
14. 14
    أخرىthe reaction liquid
15. 15
    workup.STIRRINGwas stirred at room temperature for 1 hour
16. 16
    استخلاصextracted with ethyl acetate
17. 17
    تجفيفdried with anhydrous sodium sulfate
18. 18
    أخرىThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride
19. 19
    workup.ADDITIONwere added in order to a chloroform (5 ml) solution of the resulting residue
20. 20
    أخرىthe reaction liquid
21. 21
    workup.STIRRINGwas stirred at room temperature for 30 minutes
22. 22
    استخلاصextracted with ethyl acetate
23. 23
    تجفيفdried with anhydrous sodium sulfate
24. 24
    أخرىThe solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride
25. 25
    workup.ADDITIONwere added in order to a methanol (4 ml) solution of the resulting residue
26. 26
    أخرىthe reaction liquid
27. 27
    workup.STIRRINGwas stirred at 40° C. for 1 hour
28. 28
    أخرىThe reaction liquid
29. 29
    درجة الحرارةwas cooled
30. 30
    استخلاصextracted with chloroform
31. 31
    تجفيفdried with anhydrous sodium sulfate
32. 32
    أخرىThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine
33. 33
    workup.ADDITIONwere added in order to a chloroform (4 ml) solution of the resulting residue
34. 34
    أخرىthe reaction liquid
35. 35
    workup.STIRRINGwas stirred at room temperature for 30 minutes
36. 36
    أخرىThe solvent was evaporated away under reduced pressure
37. 37
    أخرىthe resulting residue was purified
38. 38
    أخرىthrough partitioning thin-layer chromatography (chloroform/methanol=30/1)
39. 39
    أخرىto obtain a diastereomer A

الإجراء التجريبي

46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added to a chloroform (5 ml) solution of 100 mg of N-(4-(4-((t-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 22 mg of sodium azide was added to a dimethylformamide (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled, water was added to it, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution) was added to a tetrahydrofuran (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 1 hour. Water was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added in order to a chloroform (5 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride were added in order to a methanol (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 1 hour. The reaction liquid was cooled, aqueous saturated sodium bicarbonate was added to it, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine were added in order to a chloroform (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (chloroform/methanol=30/1) to obtain a diastereomer A and a diastereomer B of the entitled compound each as a colorless oily substance.

المصدر