Process for the preparation of Telmisartan
The present invention encompasses a method for the preparation of Telmisartan comprises, through Telmisartan dihydrochloride comprises i) Condensing 4-Methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid with N-Methyl-O-phenylenediamine dihydrochloride to yields 4-methyl-6 (1-methyl benzimidazol-2-yl)-2-n-propyl 1H-benzimidazole ii) Treating 4-methyl-6-(1-methylbenzimidazol-2-yl)-2-n-propyl-1H-benzimidazole with 4′-(bromomethyl)-2-biphenyl-2-carboxylate in presence of a base in an organic solvent and isolating the ester as acid addition salt iii) Converting ester acid addition salt to Telmisartan dihydrochloride and iv) Converting Telmisartan dihydrochloride to Telmisartan.
1. A process for the preparation of Telmisartan comprising:
condensing 4-Methyl-2-n-propyl-11H-benzimidazole-6-carboxylic acid with N-Methyl-O-phenylenediamine dihydrochloride in the presence of polyphosphoric acid (PPA) yields 4-methyl-6 (1-methyl benzimidazol-2-yl)-2-n-propyl 1H-benzimidazole;
treating 4-methyl-6-(1-methyl benzimidazol-2-yl)-2-n-propyl-1H-benzimidazole with 4′-(bromomethyl)-2-biphenyl-2-carboxylate in presence of a base in an organic solvent followed by treatment with mineral acid yields acid addition salt of 4′-[4-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-n-propyl-1H-benzimidazol-1-1-yl-methyl]biphenyl-2-carboxylate ester;
treating 4′-[4-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-n-propyl-1H-benzimidazol-1-yl-methyl]biphenyl-2-carboxylate ester acid addition salt with aqueous hydrochloric acid yields Telmisartan dihydrochloride; and
converting Telmisartan dihydrochloride to Telmisartan.
2. The process as claimed in claim 1 , wherein 4-methyl-6 (1-methyl benzimidazol-2-yl)-2-n-propyl 1H-benzimidazole is purified by dissolving the crude in methanol and isolating the product by adding water.
3. The process as claimed in claim 1 , wherein 4′-(bromomethyl)-2-biphenyl-2-carboxylate is its methyl ester or tert.butyl ester.
4. The process as claimed in claim 1 , wherein condensation of 4-methyl-6-(1-methyl benzimidazol-2-yl)-2-n-propyl-1H-benzimidazole with 4′-(bromomethyl)-2-biphenyl-2-carboxylate is carried out in acetone, methyl ethyl ketone or methyl isobutyl ketone.
5. The process as claimed in claim 1 , wherein condensation of 4-methyl-6-(1-methyl benzimidazol-2-yl)-2-n-propyl-1H-benzimidazole with 4′-(bromomethyl)-2-biphenyl-2-carboxylate is carried out in presence of sodium hydroxide or potassium hydroxide.
6. The process as claimed in claim 1 , wherein the obtained Telmisartan is polymorph Form-A characterized by the following:
has a melting temperature of about 269 degrees C.; and
has an IR spectrum with characteristic band at 815 cm −1 .