反应详情

温度

70 °C

To 3.43 g (14.6 mmol) 2-Methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionic acid (intermediate 1) in 38 mL toluene and 17 μL pyridine at 90° C. is added 2.60 g (21.8 mmol) SOCl2 dropwise within 20 min and stirring is continued for 2 h at 90° C. The solvent is evaporated under reduced pressure and the residue is coevaporated twice with toluene (16 mL each) to afford the crude acid cloride. To 2.00 g 2-(5-Amino-isoxazol-3-yl)-2-methyl-propionitrile (13.2 mmol, intermediate 7) in 14 mL toluene is added 3.80 mL (21.8 mmol) DIPEA. To this mixture at 60° C. is added dropwise a mixture of the acid chloride in 16 mL toluene within 10 min and stirring is continued overnight at 50° C. After addition of water (24 mL) the mixture is heated to 70° C. for 2 h and then allowed to cool to RT. The precipitate is filtered, washed with water (2×8 mL) and dried at 50° C. to afford 3.43 g of N-[3-(Cyano-dimethyl-methyl)-isoxazol-5-yl]-2-(tetrahydro-pyran-4-sulfonyl)-propionamide.

1. customThe solvent is evaporated under reduced pressure
2. customto afford the crude acid cloride
3. additionTo this mixture at 60° C. is added dropwise
4. stirringstirring
5. waitis continued overnight at 50° C
6. temperatureto cool to RT
7. filtrationThe precipitate is filtered
8. washwashed with water (2×8 mL)
9. customdried at 50° C.