The invention discloses a method for preparing LCZ696. Please see the synthesis
route in the specification. When
sodium acetate is used as alkali in the compound III preparation process, the conversion rate is high,
hydrolysis impurities are few,
system stability is good, and the reaction time is greatly shortened; in the compound I preparation process,
acetone and normal heptanes with the
mass ratio between 5 to 1and 10 to 1 serve as cocrystallization
solvent, the
reaction temperature of 35-45 DEG C is adopted, a
sodium hydroxide solution is dropwise added into a
reaction system at a certain speed at the temperature of 35-45 DEG C, generation of
hydrolysis products can be greatly reduced, the
solid precipitation state is good, purity is high,
aminolysis impurities and
hydrolysis impurities can be effectively controlled, and the LCZ696 can directly serve as
crude drug to be used for preparations.