Processes for preparation of dapagliflozin or its solvates or co-crystals thereof
AssigneeLaurus Labs Limited
InventorsUma Maheswar Rao Vasireddi, Sanjay Kumar Dehury, Madana Venkata Sudhakar Gutti, Krishna Murthy Thopudurthi
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Abstract
The present invention generally relates to an improved process for the preparation of dapagliflozin of Formula I or its solvates or co-crystals thereof. Dapagliflozin is an inhibitor of sodium dependent glucose transporters and used for treating diabetes. The present invention also encompasses novel intermediates and their use in the preparation of dapagliflozin. An exemplary process according to the present is shown below, wherein X1, R1, R2, P1, P2, P3 and P4 are as described herein.
Claims23
A process for the preparation of dapagliflozin of Formula I or its solvates or co-crystals thereof,
- comprising:
- a) (i) reacting a compound of Formula VI with a leaving group source to form a compound of Formula VIa′, (ii) reacting the compound of Formula VIa′ with an amine source in the presence of a base and a solvent to obtain a compound of Formula VII,
- wherein
- X1 and Lg each independently represent a leaving group;
- and
- R1 and R2 independently represent hydrogen, a linear or branched alkyl group, a linear or branched alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, or R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclic ring;
- b) condensing the compound of Formula VII with a glucono lactone of Formula VIII in the presence of a base and a solvent to obtain a compound of Formula IX′,
- wherein R1 and R2 are as defined above and wherein P1, P2, P3 and P4 each independently represent a hydroxyl protecting group;
- c) converting the compound of Formula IX′ to a compound of Formula XI′ with a glycosidation reagent in the presence of methanol,
- wherein P1, P2, P3, P4, R1, and R2 are as defined above;
- and
- d) reducing the compound of Formula XI′ using a reducing agent to obtain the dapagliflozin of Formula I;
- and
- e) optionally, adding a solvent to the dapagliflozin of Formula I to obtain a solvate thereof, or adding a co-crystal former to form a co-crystal thereof.
A compound of Formula VII,
- wherein
- X1 represents a leaving group;
- and
- R1 and R2 each independently represents a linear or branched alkyl group, a linear or branched alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group or R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclic ring.
A compound of Formula IX′,
- wherein R1 and R2 independently represents hydrogen, a linear or branched alkyl group, a linear or branched alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, or R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclic ring;
- and wherein P1, P2, P3 and P4 independently represents a hydroxyl protecting group.
A compound of Formula XI′
- wherein R1 and R2 independently represents hydrogen, a linear or branched alkyl group, a linear or branched alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, or R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclic ring.
Dependencies are inferred from the claim text.