The invention discloses an
Apixaban preparation method. The
Apixaban preparation method comprises that 1, an intermediate I and an intermediate II undergo a [3+2] cyclization
addition reaction under the alkali action to produce a compound B, and the compound B undergoes a
morpholine ring removal reaction under the acid condition to produce a
compound C, 2, the
compound C is reduced by
iron powder to form a corresponding amino compound D, 3, the amino compound D and 5-chlorovaleryl
chloride undergo an amidation reaction under the
triethylamine action to produce a
compound E, 4, the
compound E undergoes a cyclization reaction under the strong base action to produce a compound F, 5, the compound F undergoes a
hydrolysis reaction under the strong base action to produce a corresponding carboxyl compound G, and 6, the carboxyl compound G and CDI undergo a reaction to produce an active intermediate H and the active intermediate H and
ammonia water undergo an
aminolysis reaction to produce the desired
compound A. The
Apixaban preparation method has simple processes, does not need strict
reaction conditions, has low equipment requirements, has high reaction yield, utilizes stable intermediates thereby solving
intermediate storage problems, and effectively improves product purity.