反应详情

温度

200 °C

Ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (for a preparation, see Intermediate 16) (300 mg, 0.851 mmol) and 6-chloronicotinonitrile (236 mg, 1.702 mmol) in anhydrous NMP (5 mL) were treated with DIPEA (0.445 mL, 2.55 mmol). The reaction vial was sealed and heated under microwave irradiation to 200° C. for 2 h. The cooled solution was diluted with water to −20 mL, stirred and the resulting sticky solid isolated by decantation. The solid was dissolved in EtOAc, the solution washed with brine and dried by passing through a hydrophobic frit. The solution was concentrated in vacuo and the residue purified by MDAP (Formate) to give crude ethyl 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (120 mg) as a beige gum which was used directly in the next step without further purification. LCMS: (Formate, 2 min), Rt=1.12 min, MH+455.

1. customThe reaction
2. customvial was sealed
3. customthe resulting sticky solid isolated by decantation
4. washthe solution washed with brine
5. customdried
6. concentrationThe solution was concentrated in vacuo
7. customthe residue purified by MDAP (Formate)