Reaktion #45916

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 21.0%

Lösungsmittel

dimethyl sulfoxide

dimethyl sulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGby stirring in an oil bath at 150° C. for 30 minutes
2. 2
   SonstigeThe reaction liquid
3. 3
   Einengenwas concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
5. 5
   Waschenwashed with water and saturated brine
6. 6
   TrocknenAfter drying over anhydrous sodium sulfate
7. 7
   Sonstigethe insoluble matter was separated by filtration
8. 8
   Sonstigethe residue obtained by concentration
9. 9
   Sonstigewas 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
    Temperaturwith 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
    SonstigeThe reaction liquid
15. 15
    Einengenwas concentrated under reduced pressure
16. 16
    workup.ADDITIONan aqueous saturated sodium hydrogencarbonate solution was added
17. 17
    Extraktionfollowed by extraction with chloroform
18. 18
    TrocknenAfter drying over anhydrous sodium sulfate
19. 19
    Sonstigethe insoluble matter was separated by filtration
20. 20
    Sonstigethe residue obtained by concentration
21. 21
    Sonstigewas purified by preparative TLC (eluent, chloroform
22. 22
    Sonstigemethanol=10:1, v/v), and the obtained eluate was purified in slurry with a mixed solvent of isopropyl ether and hexane

Vorschrift

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.

Quelle