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Process For The Preparation Of Dapagliflozin And Its Solvate Thereof

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.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
15 January 2019
Publication Number
08/2019
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
cal@patentindia.com
Parent Application

Applicants

BIOCON LIMITED
20th KM, Hosur Road, Electronic City P.O., Bangalore

Inventors

1. ASWATHANARAYANAPPA, Chandrashekar
22, Panchavati Apts, 8th Cross, Pavamana Nagar Layout, Gottigere, Bannerghatta Road, Bangalore 560083
2. CHANDRA KUMAR, Sateesh, Rotte
8-41-10/2, Hemanagar, Boduppal, Hyderabad 500039
3. SHIVALINGAPPA, Manjunatha
51, Kanchiganahal, Channagiri, Davanagere 577215
4. CHARYULU, Palle Venkata, Raghavendra
5-194/A, Mythri Nagar, Madinaguda, Miyapur, Hyderabad 500049
5. SHEKHARAPPA, Bheema Rao, Begur
1st Floor, Shivasadana, Near Channel Bridge, 60 Feet Road, Vinobanagar, Shivamogga 577204
6. VENKAT, Nookaappa, Rao Gorli
120-9, Gopalapuram, Anakapalli Mandal, Vishakaptnam 531001

Specification

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%.

Documents

Application Documents

# 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

Search Strategy

1 SearchE_09-11-2020.pdf