- AN IMPROVED PURIFICATION PROCESS FOR THE PREPARATION OF ERTUGLIFLOZIN AND ERTUGLIFLOZIN L-PYROGLUTAMIC ACID CO-CRYSTAL
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The present invention relates to an improved purification process for the preparation of Ertugliflozin (I) and its further conversion to Ertugliflozin L-pyroglutamic acid (L-PGA) co-crystal (II).
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Page/Page column 18; 17
(2022/01/04)
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- AN EFFICIENT PROCESS FOR THE PREPARATION OF ERTUGLIFLOZIN L-PYROGLUTAMIC ACID AND INTERMEDIATES THEREOF
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The present invention relates to an efficient process for the preparation of Ertugliflozin L-pyroglutamic acid of formula (I) and intermediate thereof, in environment friendly conditions. The present invention further relates to a process for the preparation of substantially pure intermediate of formula (IV).
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- AMORPHOUS ERTUGLIFLOZIN AND PROCESS FOR ITS PREPARATION
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An amorphous form of ertugliflozin and process for its preparation is described. A solid form of ertugliflozin and process for preparation thereof is also described.
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- A NOVEL PROCESS FOR THE PREPARATION OF SGLT-2 INHIBITORS
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The present invention relates to a novel process for the preparation of SGLT-2 inhibitors via addition of a hydroxymethylene group in an open chain intermediate, readily accessible from D-glucose.
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- Studies towards the synthesis of ertugliflozin from L-Arabinose
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A new method for the diastereoselective synthesis of enantiomerically pure ertugliflozin was developed. The crucial step involves an aldol condensation between 1-(4-chloro-3-(4-ethoxybenzyl)phenyl)ethanone and (4R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyl-5-((trityloxy)methyl)-1,3-dioxolane-4-carbaldehyde, which was prepared from known 2-C-trityloxymethyl-2,3-O-isopropylidene-L-erythrose (easily accessible in three steps from L-arabinose) by standard reduction/oxidation and protection/deprotection manipulations. Dihydroxylation of the aldol condensation product and further global deprotection led to the formation of the target molecule.
- Triantakonstanti, Virginia V.,Mountanea, Olga G.,Papoulidou, Kyriaki-Eleni C.,Andreou, Thanos,Koftis, Theocharis V.,Gallos, John K.
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p. 5700 - 5708
(2018/08/20)
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- Preparation method of sodium-glucose cotransporter 2 inhibitor
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The invention discloses a preparation method of a sodium-glucose cotransporter 2 inhibitor. The preparation method specifically relates to a reaction step for converting a compound of a formula III into a compound of a formula II by a 'one-pot method' in a palladium carbon/acid or 1,2-dichlorobenzene catalytic system, wherein the definition of each substituent in the formula II and the formula IIIare the same as that in the description. The method has simple operation and low cost, and is suitable for large-scale production.
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Paragraph 0066-0068
(2018/04/03)
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- Glucopyranosyl derivative and its use in medicine (by machine translation)
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The invention relates to a as sodium-dependent glucose transporter (SGLTs) inhibitors of the glucopyranosyl derivative, containing the pharmaceutical composition and its use in medicine, in particular of formula (I) indicated by the glucopyranosyl derivative or its pharmaceutically acceptable salt or all of its stereoisomers, or containing the pharmaceutical composition and said derivative and pharmaceutical composition for the preparation of a medicine for treating diabetes and diabetes related diseases of the use. (by machine translation)
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Paragraph 0685-0688
(2018/07/28)
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- NOVEL POLYMORPHIC FORMS OF ((1S,2S,3S,4R,5S))-2,3,4-(TRIS-BENZYLOXY)-5-(4-CHLORO-3-(4-ETHOXY-BENZYL)PHENYL)-6,8-DIOXA-BICYCLO[3.2.1]OCT-1-YL-METHANOL
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The present invention relates to novel polymorph of (( 1 S.2S.3S,4R,5S))-2,3,4-(tris- benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1]oct-1 -yl- methanol of formula (I) wherein Bn refers to benzyl. Characterized by X-ray powder diffraction pattern peaks selected form 5.7, 14.0, 15.6, 15.9, 17.3, 18.8, 19.7, 19.8, 23.0 ±0.2° 2θ. and DSC isothermal peak ranging between 99- 103°C. The invention also relates to process for the preparation of said novel crystalline Form designated as Form-G of ((1S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy- benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1]oct-1-yl-methanol of formula (I). This compound of Formula (I) is useful as an intermediate in the preparation of Ertugliflozin, which is used in the treatment of type 2 diabetes mellitus.
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Page/Page column 9; 10
(2018/03/25)
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- Preparation method of ertugliflozin and intermediate of ertugliflozin
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The invention provides a synthesis method of ertugliflozin. The route relates to a new intermediate compound 3 and a compound 5, an SGLT-2 inhibitor ertugliflozin is prepared by virtue of the new intermediate compound 3 and the compound 5, and the preparation method is simple in process route, low in cost and applicable to industrial production. (The compound 3 and the compound 5 are described in the specification.).
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Paragraph 0065; 0066; 0067; 0068
(2018/03/28)
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- PROCESSES FOR THE PREPARATION OF ERTUGLIFLOZIN
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The present invention relates to processes for the preparation of ertugliflozni. The present invention also provides compounds of Formula (III), Formula (IV), and Formula (VII), processes for their preparation, and their use for the preparation of ertugliflozin. The processes of the present invention involve protecting the ertugliflozin intermediate compound with a suitable protecting group which provides ertugliflozin having high purity and yield.
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Paragraph 0144
(2018/01/04)
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- Commercial route research and development for SGLT2 inhibitor candidate ertugliflozin
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A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations over a 12-step sequence. The dioxabicyclo[ 3.2.1]octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-D-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with L-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.
- Bowles, Paul,Brenek, Steven J.,Caron, Stephane,Do, Nga M.,Drexler, Michele T.,Duan, Shengquan,Dube, Pascal,Hansen, Eric C.,Jones, Brian P.,Jones, Kris N.,Ljubicic, Tomislav A.,Makowski, Teresa W.,Mustakis, Jason,Nelson, Jade D.,Olivier, Mark,Peng, Zhihui,Perfect, Hahdi H.,Place, David W.,Ragan, John A.,Salisbury, John J.,Stanchina, Corey L.,Vanderplas, Brian C.,Webster, Mark E.,Weekly, R. Matt
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- Development of an early-phase bulk enabling route to sodium-dependent glucose cotransporter 2 inhibitor ertugliflozin
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The development and optimization of a scalable synthesis of sodium-dependent glucose cotransporter 2 inhibitor, ertugliflozin, for the treatment of type-2 diabetes is described. Highlights of the chemistry are a concise, four-step synthesis of a structurally complex API from known intermediate 4 via persilylation-selective monodesilylation, primary alcohol oxidation, aldol-crossed-Cannizzaro reaction, and solid-phase acid-catalyzed bicyclic ketal formation. The final API was isolated as the Lpyroglutamic acid cocrystal.
- Bernhardson, David,Brandt, Thomas A.,Hulford, Catherine A.,Lehner, Richard S.,Preston, Brian R.,Price, Kristin,Sagal, John F.,Pierre, Michael J. St.,Thompson, Peter H.,Thuma, Benjamin
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- METHODS FOR PREPARING SGLT2 INHIBITORS
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This invention relates to methods for preparing a sodium-glucose transporter 2 (SGLT2) inhibitor, a cocrytalline SGLT2 and (S)-5-oxopyrrolidine-2-carboxylic acid (L-PGA) complex, and intermediates useful in the preparation of the said SGLT2 inhibitor.
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Page/Page column 30-33
(2014/10/15)
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- Stereoselective synthesis of a dioxa-bicyclo[3.2.1]octane SGLT2 inhibitor
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A promising class of SGLT2 inhibitors bearing a unique dioxa-bicyclo[3.2.1] octane motif was recently disclosed. An improved stereoselective synthesis providing efficient access to one of the most potent and selective compounds from this class is reported. A one-pot deprotection/cyclization was used as the key step to form the dioxa-bicyclo[3.2.1]octane motif with full control of stereochemistry. Using an appropriately substituted aryl group, the route enables the synthesis of any given compound from the class.
- Mascitti, Vincent,Preville, Cathy
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supporting information; experimental part
p. 2940 - 2943
(2010/09/10)
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- DIOXA-BICYCLO[3.2.1.]OCTANE-2,3,4-TRIOL DERIVATIVES
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Compounds of Formula (I) are described herein and the uses thereof for the treatment of diseases, conditions and/or disorders mediated by sodium-glucose transporter inhibitors (in particular, SGLT2 inhibitors).The compounds disclosed herein are useful for the prevention and treatment of obesity and its associated co-morbidities, inn particular type Il (type 2) diabetes.
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Page/Page column 64-66
(2010/04/06)
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