Reaktion #612323

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

2-chloroethanol

→

title compound

Ausbeute 67.8%

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

Ausbeute 67.8%

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
   ExtraktionThe organic extractions
8. 8
   Waschenwashed 3× with a dilute brine solution
9. 9
   SonstigeThe organic layer was separated
10. 10
    Trocknendried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated in vacuo
13. 13
    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)
14. 14
    workup.ADDITIONThe product fractions were neutralized with the addition of saturated aq sodium bicarbonate
15. 15
    Extraktionextracted with dichloromethane
16. 16
    TrocknenThe organic layer was dried over sodium sulfate
17. 17
    Filtrationfiltered
18. 18
    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 2-chloroethanol (24 mg, 0.299 mmol, 2.3 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 extractions 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 (41 mg, 67%). MS(ES)+ m/e 473.2 [M+H]+.

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