SYNTHESIS PROCESS OF GEMINAL BISPHOSPHONIC ACIDS OR THEIR PHARMACEUTICALLY ACCEPTABLE SALTS OR THEIR HYDRATS.

摘要

A process for preparing a geminal bisphosphonic acid or a salt or hydrate thereof comprising: a. reacting a compound of formula R 1 -C (= 0) -R 2 in the presence of: i. phosphorous acid in the presence of an alkylphosphonic anhydride; or ii. methanesulfonic anhydride; or iii. methanesulfonic acid and phosphorous acid, to form the bisphosphonic acid of the formula: ** see formula ** where: R 1 and R 2 are independently hydrogen, hydroxy or alkyl which is substituted or unsubstituted b. optionally, adjust the pH in (a.) to form the salt or hydrate of bisphosphonic acid of formula ** see formula ** c. where: R 1 and R 2 are independently hydrogen, hydroxy or alkyl that is substituted or unsubstituted; and X 1, X 2, X 3 and X 4 are independently a hydrogen or form a pharmaceutically acceptable sa optionally, purify the bisphosphonic acid or the salt or hydrate thereof.