反応 #45916

反応方程式

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

triethylamine

4-cyano-7-fluoro-6-(3-fluorophenyl)-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

→

compound

収率 21.0%

4-Cyano-6-(3-fluorophenyl)-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino)pyrrolidin-1-yl]-1,3-benzoxazole-2-carboxamide

収率 21.0%

溶媒

dimethyl sulfoxide

dimethyl sulfoxide

反応条件

後処理

1. 1
   workup.STIRRINGby stirring in an oil bath at 150° C. for 30 minutes
2. 2
   その他The reaction liquid
3. 3
   濃縮was concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
5. 5
   洗浄washed with water and saturated brine
6. 6
   乾燥After drying over anhydrous sodium sulfate
7. 7
   その他the insoluble matter was separated by filtration
8. 8
   その他the residue obtained by concentration
9. 9
   その他was purified by silica gel column chromatography (eluent, n-hexane
10. 10
    workup.DISSOLUTIONThe obtained yellow foamy substance was dissolved in dichloromethane (3 ml)
11. 11
    温度with cooling with ice, trifluoroacetic acid (6 ml)
12. 12
    workup.ADDITIONwas added
13. 13
    workup.STIRRINGby stirring at room temperature for 8 hours
14. 14
    その他The reaction liquid
15. 15
    濃縮was concentrated under reduced pressure
16. 16
    workup.ADDITIONan aqueous saturated sodium hydrogencarbonate solution was added
17. 17
    抽出followed by extraction with chloroform
18. 18
    乾燥After drying over anhydrous sodium sulfate
19. 19
    その他the insoluble matter was separated by filtration
20. 20
    その他the residue obtained by concentration
21. 21
    その他was purified by preparative TLC (eluent, chloroform
22. 22
    その他methanol=10:1, v/v), and the obtained eluate was purified in slurry with a mixed solvent of isopropyl ether and hexane

実験手順

A dimethyl sulfoxide (0.5 ml) solution of the above-mentioned tert-butyl methyl[(3S)-3-methylpyrrolidin-3-yl]carbamate (I-348) and triethylamine (172 μl, 1.23 mmol) was added to a dimethyl sulfoxide (4.5 ml) solution of 4-cyano-7-fluoro-6-(3-fluorophenyl)-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-184) (300 mg, 0.878 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 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 (3 ml), and with cooling with ice, trifluoroacetic acid (6 ml) was added, followed by stirring at room temperature for 8 hours. The reaction liquid was concentrated under reduced pressure, then an aqueous saturated sodium hydrogencarbonate solution was 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 a mixed solvent of isopropyl ether and hexane to obtain the entitled compound (80.0 mg, 21%) as a pale yellow solid.

出典