Réaction #161803

Équation de réaction

potassium carbonate

1-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one dihydrochloride

(2-chloropyridin-4-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone

DIPEA

→

1-[4′-(5-fluoro-2,3-dihydroindole-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1.2′]bipyridinyl-4-yl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one

Solvants

water

N-methylpyrrolidone

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGthe reaction mixture was stirred for a further 24 h at 130° C
2. 2
   Extractionextracted with EtOAc (3×100 mL)
3. 3
   AutreThe combined organic phases were dried
4. 4
   Autreevaporated
5. 5
   Autrethe rotary evaporator
6. 6
   AutreThe residue was purified by preparative HPLC
7. 7
   Autreevaporated down i
8. 8
   AutreThe residue was triturated with 30 mL diethyl ether
9. 9
   Filtrationfiltered
10. 10
    Autredried in the air

Mode opératoire

232 mg (0.8 mmol) 1-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one dihydrochloride were added to 220 mg (0.80 mmol) (2-chloropyridin-4-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone and 0.52 mL (3.00 mmol) DIPEA in 3.0 mL N-methylpyrrolidone. The reaction mixture was stirred for 6 h at 130° C. After 4 h 400 mg potassium carbonate were added and the reaction mixture was stirred for a further 24 h at 130° C. Then the mixture was poured onto 100 mL water and extracted with EtOAc (3×100 mL). The combined organic phases were dried and evaporated down using the rotary evaporator. The residue was purified by preparative HPLC. The product fractions were combined and evaporated down i. vac. The residue was triturated with 30 mL diethyl ether. The precipitated solid was suction filtered and dried in the air.

Source