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

HRID 525139

Reaktionsgleichung

Reaktionsgleichung von HRID 525139
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[C:20]([CH2:21][C@@H:22]5[CH2:26][CH2:25][N:24]([C:27]([CH:29]6[CH2:31][CH2:30]6)=[O:28])[CH2:23]5)=[N:19][NH:18][C:17]4=[O:32])=[CH:12][CH:11]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:39][O:40][CH2:41][CH2:42]Cl>CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:11]=[CH:12][C:13]([N:16]4[C:20]([CH2:21][C@@H:22]5[CH2:26][CH2:25][N:24]([C:27]([CH:29]6[CH2:30][CH2:31]6)=[O:28])[CH2:23]5)=[N:19][N:18]([CH2:42][CH2:41][O:40][CH3:39])[C:17]4=[O:32])=[CH:14][CH:15]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 123162-Chloroethyl methyl etherHCID 67376285Gsk2194069

Produkt 1

HCID 682609364-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2-[2-(methyloxy)ethyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneAusbeute 35,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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 (60 mg, 0.14 mmol) in N,N-dimethylformamide (1 mL) in a 5 mL microwaveable vial was added potassium carbonate (60 mg, 0.434 mmol, 3.1 eq) and 2-chloroethyl methyl ether (21 mg, 0.220 mmol, 1.5 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 progressed to 80% 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; 25-65% 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 (24 mg, 33%). MS(ES)+ m/e 487.3 [M+H]+.

Aufarbeitung

  1. customThe vial was capped
  2. custompurged with nitrogen gas
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionpoured into a mixture of dichloromethane and water
  5. customThe organic layer was separated
  6. washThe aqueous layer was washed with dichloromethane
  7. washwashed 3× with a dilute brine solution
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 25-65% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  13. additionThe product fractions were neutralized with the addition of saturated aq sodium bicarbonate
  14. extractionextracted with dichloromethane
  15. dry with materialThe organic layer was dried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e12b516b5ffe490e85b9b8d7d9228da7
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340529B2

Verknüpfte Notizen

Wird geladen…