反应详情

2,6-Dichloro-4-trifluoromethyl-nicotinonitrile (277 mg, 1.15 mmol) was dissolved into 10 mL of absolute EtOH and cooled in a wet ice bath. To this was added DIPEA (1.74 mL, 10 mmol) and 1-(1-methyl-1H-benzoimidazol-2-yl)-2-(piperidin-4-ylamino)-ethanol dihydrochloride (400 mg, 1.15 mmol). The mixture was stirred for 2 h. LC-MS anlysis indicated formation of the product. The reaction mixture was concentrated on a rotary evaporator and the residue was dissolved in CH2Cl2 and applied to a SiO2 column and purified (0–10% MeOH/CH2Cl2) to give an oil, still contaminated with DIPEA. Trituration with EtOAc gave 344 mg, 62.4% of 6′-chloro4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile.

1. temperaturecooled in a wet ice bath
2. concentrationThe reaction mixture was concentrated on a rotary evaporator
3. dissolutionthe residue was dissolved in CH2Cl2
4. custompurified (0–10% MeOH/CH2Cl2)
5. customto give an oil