Reaktion #612322

Reaktionsgleichung

4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

potassium carbonate

methyl chloroacetate

→

title compound

Ausbeute 57.7%

methyl (4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetate

Ausbeute 57.7%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe vial was capped
2. 2
   Sonstigepurged with nitrogen gas
3. 3
   TemperaturThe reaction mixture was cooled to room temperature
4. 4
   workup.ADDITIONpoured into a mixture of dichloromethane and water
5. 5
   SonstigeThe organic layer was separated
6. 6
   WaschenThe aqueous layer was washed with dichloromethane
7. 7
   Waschenwashed 3× with a dilute brine solution
8. 8
   SonstigeThe organic layer was separated
9. 9
   Trocknendried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo
12. 12
    SonstigeThe crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-55% acetonitrile w/0.1% TFA/water w/0.1% TFA)
13. 13
    workup.ADDITIONThe product fractions were neutralized with the addition of saturated aq sodium bicarbonate
14. 14
    Extraktionextracted with dichloromethane
15. 15
    TrocknenThe organic layer was dried over sodium sulfate
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated in vacuo

Vorschrift

To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (55 mg, 0.128 mmol) in N,N-dimethylformamide (1 mL) in a 5 mL microwaveable vial was added potassium carbonate (60 mg, 0.434 mmol, 3.3 eq) and methyl chloroacetate (25 mg, 0.227 mmol, 1.7 eq). The vial was capped and purged with nitrogen gas, and the reaction mixture was stirred for 16 h at 80° C. Analysis by LC/MS displayed the reaction had gone to completion. The reaction mixture was cooled to room temperature and poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extracts were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-55% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (37 mg, 57%). MS(ES)+ m/e 501.1 [M+H]+.

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