반응 #45918

반응 방정식

tert-butyl [(3S)-3-methylpyrrolidin-3-yl]carbamate

triethylamine

4-cyano-7-fluoro-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

→

compound

수율 41.6%

7-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-4-cyano-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

수율 41.6%

용매

dimethyl sulfoxide

dimethyl sulfoxide

반응 조건

후처리

1. 1
   workup.STIRRINGby stirring in an oil bath at 150° C. for 30 minutes
2. 2
   기타The reaction liquid
3. 3
   농축was concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
5. 5
   세척washed with aqueous 10% citric acid solution, water and saturated brine
6. 6
   건조After drying over anhydrous sodium sulfate
7. 7
   기타the insoluble matter was separated by filtration
8. 8
   기타the residue obtained by concentration
9. 9
   기타was purified by silica gel column chromatography (eluent, n-hexane
10. 10
    workup.DISSOLUTIONThe obtained yellow foamy substance was dissolved in dichloromethane (5 ml)
11. 11
    온도with cooling with ice, trifluoroacetic acid (10 ml)
12. 12
    workup.ADDITIONwas added
13. 13
    workup.STIRRINGby stirring at room temperature for 5 hours
14. 14
    기타The reaction liquid
15. 15
    농축was concentrated under reduced pressure
16. 16
    workup.ADDITIONan aqueous saturated sodium hydrogencarbonate solution and water were added
17. 17
    추출followed by extraction with chloroform
18. 18
    건조After drying over anhydrous sodium sulfate
19. 19
    기타the insoluble matter was separated by filtration
20. 20
    기타the residue obtained by concentration
21. 21
    기타was purified by preparative TLC (eluent, chloroform
22. 22
    기타methanol=10:1, v/v), and the obtained eluate was purified in slurry with isopropyl ether

실험 절차

A dimethyl sulfoxide (1 ml) solution of tert-butyl [(3S)-3-methylpyrrolidin-3-yl]carbamate (I-345) (300 mg, 1.50 mmol) and triethylamine (244 μl, 1.75 mmol) was added to a dimethyl sulfoxide (6 ml) solution of 4-cyano-7-fluoro-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-114) (404 mg, 1.25 mmol) stirred in an oil bath at 150° C., followed by stirring in an oil bath at 150° C. for 30 minutes. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with aqueous 10% citric acid solution, water and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=1:1→1:2, v/v). The obtained yellow foamy substance was dissolved in dichloromethane (5 ml), and with cooling with ice, trifluoroacetic acid (10 ml) was added, followed by stirring at room temperature for 5 hours. The reaction liquid was concentrated under reduced pressure, then an aqueous saturated sodium hydrogencarbonate solution and water were added, followed by extraction with chloroform. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, the residue obtained by concentration was purified by preparative TLC (eluent, chloroform:methanol=10:1, v/v), and the obtained eluate was purified in slurry with isopropyl ether to obtain the entitled compound (210 mg, 41%) as a pale yellow solid.

출처