Process for preparation of indacaterol or its pharmaceutically acceptable salts
A novel process the for preparation of Indacaterol or its pharmaceutically acceptable salts and novel intermediates employed in the preparation thereof that is economically significant for large scale.
1. A process for preparation of Indacaterol free base or its pharmaceutically acceptable salt comprising the steps of:
i) treating the compound of formula II
with the reducing agent to obtain compound of formula III
where L is good leaving group;
ii) treating compound of formula III with silylated protecting reagent to obtain compound of formula IV
where A is silylated protective group;
iii) reacting the compound of formula IV with compound of formula V or its derivatives in the presence of a base
to obtain compound of formula VI,
iv) desilylating compound of formula VI to obtain compound of formula VII
v) debenzylating the compound of formula VII to obtain compound of formula I Indacaterol free base
vi) optionally converting the compound of formula I into its pharmaceutically acceptable salts.
2. A process for the preparation of compound of formula VI
comprising the step of:
i) reacting the compound of formula IV
with compound of formula V or its derivatives in the presence of base,
to obtain compound of formula VI, wherein A is silylated protective group.
3. The process as claimed in claim 1 , wherein reducing agent used in step (i) is R-Methyl CBS.
4. The process as claimed in claim 1 , wherein silylating agent used in step (ii) is tert-Butyldimethylsilyl chloride (TBDMSCl).
5. The process as claimed in claim 1 , wherein base used in step (iii) is N-methyl pyrrolidone.
6. The process as claimed in claim 1 , where in desilylating agent used in step (iv) is tetra-n-butylammonium fluoride.
7. The process as claimed in claim 1 , where in debenzylating agent used in step (v) is palladium with carbon.
8. The process as claimed in claim 1 , where in solvents used in step (i) to step (vi) are methanol, tetrahydrofuran, chloroform, ethyl acetate, methylene dichloride and isopropyl alcohol.
9. The process as claimed in claim 2 , wherein base used in step (i) is N-methyl pyrrolidone.
10. The process as claimed in claim 2 , wherein the reaction in step (i) takes place at a temperature between 95° C. to 100° C.