Reaktion #2492533

Reaktionsgleichung

HCl

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

(3-fluoro-4-methylphenyl)boronic acid

water

→

title compound

Ausbeute 58.0%

5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(3,3′-difluoro-4′-methyl-4-biphenylyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Ausbeute 58.0%

Lösungsmittel

dioxane

potassium carbonate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas irradiated in the microwave at 150° C. for 15 min
2. 2
   ExtraktionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
3. 3
   Trocknenthe combined organic layers were dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigePurification of the residue by flash chromatography (100% ethyl acetate)

Vorschrift

A mixture of 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.244 mmol), (3-fluoro-4-methylphenyl)boronic acid (0.370 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.012 mmol) in dioxane (2.0 mL) and 2M aq potassium carbonate (0.5 mL) was irradiated in the microwave at 150° C. for 15 min. The reaction mixture was poured into water (50 mL) and the pH was adjusted to 5 with addition of 1N aq HCl. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (100% ethyl acetate) and then reverse phase HPLC (30-65% acetonitrile/water with 0.1% NH4OH) provided the title compound as a tan solid (58%). MS(ES)+ m/e 439.2 [M+H]+.

Quelle