Reaction #161803

Reaction equation

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

Solvents

water

N-methylpyrrolidone

Conditions

Workup

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
   OtherThe combined organic phases were dried
4. 4
   Otherevaporated
5. 5
   Otherthe rotary evaporator
6. 6
   OtherThe residue was purified by preparative HPLC
7. 7
   Otherevaporated down i
8. 8
   OtherThe residue was triturated with 30 mL diethyl ether
9. 9
   Filtrationfiltered
10. 10
    Otherdried in the air

Procedure

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