Reaction #45917

Reaction equation

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

triethylamine

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

→

compound

Yield 21.1%

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

Yield 21.1%

Solvents

dimethyl sulfoxide

dimethyl sulfoxide

Conditions

Workup

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

Procedure

A dimethyl sulfoxide (1 ml) solution of tert-butyl methyl[(3S)-3-methylpyrrolidin-3-yl]carbamate (I-348) (318 mg, 1.48 mmol) and triethylamine (241 μl, 1.73 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) (400 mg, 1.24 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, 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 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 recrystallized from isopropyl ether to obtain the entitled compound (109 mg, 21%) as a pale yellow solid.

Source