Process for rilpivirine
AssigneeHetero Research Foundation
InventorsBandi Parthasaradhi Reddy, Kura Rathnakar Reddy, Dasari Muralidhara Reddy, Adulla Venkat Narsimha Reddy, Bandi Vamsi Krishna
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Abstract
The present invention provides a novel process for the preparation of 4-(4-hydroxypyrimidin-2-ylamino)benzonitrile. The present invention also provides a novel process for the preparation of 4-iodo-2,6-dimethyl benzenamine. The present invention further provides an improved process for the preparation of rilpivirine. The present invention further provides a tosylate salt of rilpivirine, process for its preparation and pharmaceutical compositions comprising it.
Claims25
A process for the preparation of 4-(4-chloropyrimidin-2-ylamino)benzonitrile of formula I, which comprises:
- a. condensing the 2-chloro-4-methoxypyrimidine with 4-aminobenzonitrile in the presence of p-toluene sulfonic acid in an ether solvent;
- b. reacting the 4-(4-methoxypyrimidin-2ylamino)benzonitrile with pyridine hydrochloride in the presence of a nitrile solvent to obtain 4-(4-hydroxypyrimidin-2ylamino)benzonitrile;
- and
- c. reacting the 4-(4-hydroxypyrimidin-2ylamino)benzonitrile with pyridine hydrochloride obtained in step (a) with phosphorous oxychloride in the presence of an alcoholic solvent to obtain a compound of formula I.
A process for the preparation of 4-iodo-2,6-dimethyl aniline, which comprises reacting the 2,6-dimethyl aniline with iodine in the presence of a base and a solvent.
A process for the preparation of rilpivirine, which comprises:
- a. reacting the 4-(4-chloropyrimidin-2-ylamino)benzonitrile with (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile hydrochloride in the presence of p-toluene sulfonic acid monohydrate and an ether solvent;
- b. heating the contents obtained in step (a) at above 90° C. to obtain a solution;
- c. cooling the solution obtained in step (b) at below 35° C.;
- d. basifying the solution with a base;
- e. extracting rilpivirine into organic solvent;
- f. removing the solvent from the solution obtained in step (e) to obtain a solid;
- g. slurrying the solid obtained in step (f) with a ketonic solvent, a nitrile solvent or mixture thereof;
- and
- h. isolating rilpivirine.
A tosylate salt of rilpivirine.
A process for the preparation of tosylate salt of rilpivirine, which comprises:
- a. dissolving rilpivirine in a ketonic solvent;
- b. adding p-toluene sulfonic acid to the solution obtained in step (a);
- and
- c. isolating tosylate salt of rilpivirine.
A pharmaceutical composition that comprises tosylate salt of rilpivirine and pharmaceutically acceptable excipients, and optionally other therapeutic ingredients.
Dependencies are inferred from the claim text.