Reaction #40574

Reaction equation

6-(2-chloropyrimidin-4-yl)-2-(2-trimethylsilanylethoxymethyl)-4-[1-(2-trimethylsilanylethoxymethyl)-1H-benzimidazol-2-yl]-2H-pyridazin-3-one

cyclopropylboronic acid

potassium phosphate

→

6-(2-Cyclopropylpyrimidin-4-yl)-2-(2-trimethylsilanylethoxymethyl)-4-[1-(2-trimethylsilanylethoxymethyl)-1H-benzimidazol-2-yl]-2H-pyridazin-3-one

Solvents

toluene

water

water

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Extractionextracted several times with ethyl acetate
3. 3
   Extractionthe combined organic phases are extracted once more with saturated sodium chloride solution
4. 4
   Otherdried
5. 5
   OtherThe crude product is purified by RP HPLC (acetonitrile (+0.05% HCOOH)/water (+0.05% HCOOH))

Procedure

100 mg of 6-(2-chloropyrimidin-4-yl)-2-(2-trimethylsilanylethoxymethyl)-4-[1-(2-trimethylsilanylethoxymethyl)-1H-benzimidazol-2-yl]-2H-pyridazin-3-one, 29.2 mg of cyclopropylboronic acid and 138 mg of potassium phosphate are dissolved in 1 ml of toluene and 0.05 ml of water and, under an argon atmosphere, 17 mg of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride (1:1 complex with CH2Cl2) are added. The mixture is stirred at 100° C. for 9 h. After cooling to room temperature, it is diluted with 15 ml of water and extracted several times with ethyl acetate, and the combined organic phases are extracted once more with saturated sodium chloride solution and dried using a Varian Chem Elut CE 1005 cartridge. The crude product is purified by RP HPLC (acetonitrile (+0.05% HCOOH)/water (+0.05% HCOOH)).

Source