Abstract: The present invention provides for crystalline Dapagliflozin butane -12- diol solvate (VIII) crystalline Dapagliflozin (S) butane -12- diol solvate (VIIIa) and Dapagliflozin (R) butane -12- diol solvate (VIIIb). The present invention also provides industrial methods for production of crystalline Dapagliflozin butane -12- diol solvate (VIII) crystalline 5 Dapagliflozin (S) butane -12- diol solvate (VIIIa) and Dapagliflozin (R) butane -12- diol solvate (VIIIb). The present invention further provides an industrial method production of amorphous Dapagliflozin.
1. A process for the preparation of crystalline Dapagliflozin 1,2-butanediol solvate, comprising:
a) Hydrolysing a compound of formula VI to a compound of formula VII i n presence of a base using a biphasic solvent medium
b) Separating the layers
c) Adding 1,2-butanediol and water to the compound VII
d) Isolating crystalline Dapagliflozin 1,2-butanediol solvate.
2. Dapagliflozin 1,2-butanediol solvate.
3. A crystalline Dapagliflozin 1,2-butanediol solvate.
4. A crystalline Dapagliflozin 1,2-butanediol solvate of claim 3, characterized by an X-ray powder diffraction (XRPD) spectrum having peak reflections at about 3.9, 15.2, 15.7, 17.1, 19.0, 20.0, 20.3 and 21.6 e0.2 degrees 2 theta.
5. Dapagliflozin 1,2-butanediol solvate of any of the preceding claims in the form of monohydrate.
6. Dapagliflozin (S) - 1,2-butanediol solvate.
7. A crystalline Dapagliflozin (S) - 1,2-butanediol solvate.
8. A crystalline Dapagliflozin (S)- 1,2-butanediol solvate of claim7, characterized by an X-ray powder diffraction (XRPD) spectrum having peak reflections at about 3.7, 15.1, 17.0, 18.9, 19.7 and 21.3 eO.2 degrees 2 theta.
9. A process for the preparation of crystalline Dapagliflozin (S)- 1,2-butanediol solvate, the process comprisi ng:
a) Hydrolysing a compound of formula VI to a compound of formula VII in presence of a base using a bi phasic solvent medium
b) Separating the layers
c) Adding (S)-1,2-butanediol and water to the compound VII
d) Isolating crystalline Dapagliflozin (S)- 1,2-butanediol solvate.
10. Dapagliflozin (S) - 1,2-butanediol solvate of any of the preceding claims 6 to 9 in the form of monohydrate.
11. Dapagliflozin (R) - 1,2-butanediol solvate.
12. A process for the preparation of Dapagliflozin (R)- 1,2-butanediol solvate, the process comprising:
a) Hydrolysing a compound of formula VI to a compound of formula VII i n presence of a base using a biphasic solvent medium
b) Separating the layers
c) Adding (R)-1,2-butanediol and water to the compound VII
d) Isolating Dapagliflozin (R)- 1,2-butanediol solvate.
13. A process for the preparation of Dapagliflozin amorphous form, the process comprising:
a) Hydrolysing a compound of formula VI to a compound of formula VII in presence of a base and using a bi phasic solvent medium
b) Separating the layers
c) Isolating the amorphous Dapagliflozin.
14. Biphasic solvent medium according to any of the preceding claims comprising n-butanol-water, methyl ethyl ketone-water, methyl isobutyl ketone "water, methyl tert-butyl ether "water toluene-water and the like.
15. Biphasic solvent medium according claim 14 comprising n-butanol-water.
16. A compound 2-(4-chloro-3-(4-ethoxybenzyl) phenyl)-6-(hydroxymethyl)-4H-pyran-4-one of formula XIII.
17. A compound (2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl) phenyl) (4-ethoxyphenyl) methanone of formula XIV.
18. A process for the preparation of Dapagliflozin- 1,2-butanediol solvate from crude Dapagl if I ozin without subjecting to acetylation step.
19. A process for the preparation of Dapagliflozin (S)- 1,2-butanediol solvate from crude Dapagliflozin without subjecting to acetylation step.
20. A process for the preparation of Dapagliflozin (R)- 1,2-butanediol solvate from crude Dapagliflozin without subjecting to acetylation step.
21. A process for preparation of amorphous Dapagliflozin compound from Dapagliflozin -1,2-butanediol solvate.
22. A process for preparation of amorphous Dapagliflozin compound from Dapagliflozin (S)- 1,2-butanediol solvate.
23. A process for preparation of amorphous Dapagliflozin compound from Dapagliflozin (R)- 1,2-butanediol solvate.
24. Highly pure CrystalIine Dapagliflozin- 1,2-butanediol solvate wherein impurity 2-(4-chloro-3-(4-ethoxybenzyl) phenyl)-6-(hydroxymethyl)-4H-pyran-4-one of formula XIII is less than 0.15%.
25. Highly pure Crystalline Dapagliflozin- 1,2-butanediol solvate wherein impurity (2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl) phenyl) (4-ethoxyphenyl) methanone of formula XIV is less than 0.15 %.
26. Highly pure Crystalline Dapagliflozin- 1,2-butanediol solvate wherein impurity ((2R,3S,4R,5R,6S)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate of formula XV is less than 0.15 %.
27. Highly pure Crystalline Dapagliflozin (S)- 1,2-butanediol solvate wherein impurity 2-(4-chloro-3-(4-ethoxybenzyl) phenyl)-6-(hydroxymethyl)-4H-pyran-4-one of formula XIII is less than 0.15%.
28. Highly pure Crystalline Dapagliflozin (S)- 1,2-butanediol solvate wherein impurity (2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl) phenyl) (4-ethoxyphenyl) methanone of formula XIV is less than 0.15 %.
hSHighly pure Crystalline Dapagliflozin (S)- 1,2-butanediol solvate wherein impurity ((2R,3S,4R,5R,6S)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl) methyl acetate of formula XV is less than 0.15%.
| # | Name | Date |
|---|---|---|
| 1 | 201947001766-FER.pdf | 2021-10-17 |
| 1 | 201947001766.pdf | 2019-01-15 |
| 2 | 201947001766-STATEMENT OF UNDERTAKING (FORM 3) [15-01-2019(online)].pdf | 2019-01-15 |
| 2 | 201947001766-FORM 18 [23-06-2020(online)].pdf | 2020-06-23 |
| 3 | 201947001766-PRIORITY DOCUMENTS [15-01-2019(online)].pdf | 2019-01-15 |
| 3 | 201947001766-AMMENDED DOCUMENTS [22-06-2020(online)].pdf | 2020-06-22 |
| 4 | 201947001766-FORM 13 [22-06-2020(online)].pdf | 2020-06-22 |
| 4 | 201947001766-FORM 1 [15-01-2019(online)].pdf | 2019-01-15 |
| 5 | 201947001766-MARKED COPIES OF AMENDEMENTS [22-06-2020(online)].pdf | 2020-06-22 |
| 5 | 201947001766-DRAWINGS [15-01-2019(online)].jpg | 2019-01-15 |
| 6 | Correspondence by Agent_Form1,Power of Attorney_14-03-2019.pdf | 2019-03-14 |
| 6 | 201947001766-DECLARATION OF INVENTORSHIP (FORM 5) [15-01-2019(online)].pdf | 2019-01-15 |
| 7 | 201947001766-FORM-26 [08-03-2019(online)].pdf | 2019-03-08 |
| 7 | 201947001766-COMPLETE SPECIFICATION [15-01-2019(online)].pdf | 2019-01-15 |
| 8 | 201947001766-Proof of Right (MANDATORY) [07-03-2019(online)].pdf | 2019-03-07 |
| 9 | 201947001766-FORM-26 [08-03-2019(online)].pdf | 2019-03-08 |
| 9 | 201947001766-COMPLETE SPECIFICATION [15-01-2019(online)].pdf | 2019-01-15 |
| 10 | 201947001766-DECLARATION OF INVENTORSHIP (FORM 5) [15-01-2019(online)].pdf | 2019-01-15 |
| 10 | Correspondence by Agent_Form1,Power of Attorney_14-03-2019.pdf | 2019-03-14 |
| 11 | 201947001766-MARKED COPIES OF AMENDEMENTS [22-06-2020(online)].pdf | 2020-06-22 |
| 11 | 201947001766-DRAWINGS [15-01-2019(online)].jpg | 2019-01-15 |
| 12 | 201947001766-FORM 13 [22-06-2020(online)].pdf | 2020-06-22 |
| 12 | 201947001766-FORM 1 [15-01-2019(online)].pdf | 2019-01-15 |
| 13 | 201947001766-PRIORITY DOCUMENTS [15-01-2019(online)].pdf | 2019-01-15 |
| 13 | 201947001766-AMMENDED DOCUMENTS [22-06-2020(online)].pdf | 2020-06-22 |
| 14 | 201947001766-STATEMENT OF UNDERTAKING (FORM 3) [15-01-2019(online)].pdf | 2019-01-15 |
| 14 | 201947001766-FORM 18 [23-06-2020(online)].pdf | 2020-06-23 |
| 15 | 201947001766.pdf | 2019-01-15 |
| 15 | 201947001766-FER.pdf | 2021-10-17 |
| 1 | SearchE_09-11-2020.pdf |