Processes for the preparation of empagliflozin
AssigneeCadila Healthcare Limited
InventorsSanjay Jagdish DESAI, Jayprakash Ajitsingh PARIHAR, Mahesh Laljibhai RUPAPARA, Pranav Jitendra GANGWAR, Hardik Bhikhubhai GHODASARA
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Abstract
The present invention relates to processes for the preparation of empagliflozin. In particular, the present invention relates to the preparation of empagliflozin and intermediates thereof. The present invention also relates to co-crystal of empagliflozin and amino acid and amorphous form of empagliflozin.
Claims22
A compound of general Formula (II-SH),
- wherein n is 0.5 to 2, X is C3 to C6 ketone.
A cocrystal of empagliflozin and amino acid selected from L-proline, L-threonine, L-cysteine, L-methionine, L-phenylalanine, L-tyrosine, L-asparagine, L-aspartic acid, L-glutamine, L-glutamic acid, L-lysine, L-arginine, L-histidine, L-serine, L-tryptophan, L-alanine, L-valine, L-leusine, L-isoleusine, D-asparagine, D-aspartic acid, D-glutamine, D-phenylalanine, D-alanine, D-valine, D-leusine, D-glutamic acid, D-arginine, D-serine, D-threonine, D-methionine, D-isoleusine and D-proline.
A process for the preparation of an amorphous form of empagliflozin, the process comprising:
- (a) dissolving cocrystal of empagliflozin and L-proline in one or more solvents;
- (b) removing the solvents to obtain a residue;
- (c) dissolving the residue in one or more another solvent;
- and
- (d) removing the solvent to obtain the amorphous form of empagliflozin.
A compound of Formula (VI)
- wherein R is a protecting group selected from trityl, allyl or tetrahydropyran.
A compound of Formula (VI-a)
A compound of Formula (IV-P)
A process for the preparation of empagliflozin, the process comprising:
- (a) reacting 5-bromo-2-chloro-4′-ethoxydiphenylmethane of Formula (VIII) with Lewis acid to obtain 5-bromo-2-chloro-4′-hydroxydiphenylmethane of Formula (VII);
- (b) reacting 5-bromo-2-chloro-4′-hydroxydiphenylmethane of Formula (VII) with a hydroxy protecting reagent to obtain a compound of Formula (VI);
- (c) reacting the compound of Formula (VI) with a compound of Formula (P-G) to obtain a compound of Formula (V);
- (d) converting the compound of Formula (V) into a compound of Formula (II-SH);
- wherein n is 0.5 to 2, X is C3 to C6 ketone,
- (e) converting the compound of the Formula (II-SH) into a compound of Formula (C);
- and
- (f) converting the compound of Formula (C) into empagliflozin.
Empagliflozin substantially free from one or more of impurities selected from diastereomer impurity, dialkylated impurity, furoanose impurity-1, Furanose impurity-2 and monoacetylated empagliflozin as determined by area percentage of HPLC.
A pharmaceutical composition comprising amorphous empagliflozin substantially free from one or more impurities according to claim 22 and one pharmaceutically acceptable excipients, diluents or carriers.
Dependencies are inferred from the claim text.