- Synthesis of empagliflozin, a novel and selective sodium-glucose co-transporter-2 inhibitor, labeled with carbon-14 and carbon-13
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Empagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5- triol was recently approved by the FDA for the treatment of chronic type 2 diabetes mellitus. Herein, we report the synthesis of car
- Hrapchak, Matt,Latli, Bachir,Wang, Xiao-Jun,Lee, Heewon,Campbell, Scot,Song, Jinhua J.,Senanayake, Chris H.
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Read Online
- PREPARATION OF HIGHLY PURE AMORPHOUS DAPAGLIFLOZIN
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A novel and improved process for the preparation of amorphous dapagliflozin is disclosed. The present invention further provides pharmaceutical compositions containing amorphous dapagliflozin, optionally in a combination with one or more other active substances and methods for making the same.
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Page/Page column 23
(2021/12/13)
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- Synthetic method of empagliflozin
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The invention provides a brand-new synthesis process of empagliflozin. According to the process, a boric acid ester is used for halogen removal, and specific reaction conditions are combined, so thatempagliflozin can be prepared with high yield and simplicity and convenience in operation. The synthesis method of empagliflozin has the advantages of mild reaction conditions, high total yield, few side reactions and convenience in operation, thereby being beneficial to industrial production and cost control.
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Paragraph 0068-0070
(2020/02/14)
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- Synthesis method of dapagliflozin intermediate 5-bromo-2-chloro-4 '-ethoxydiphenylmethane
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The invention discloses a synthesis method of a dapagliflozin intermediate 5-bromo-2-chloro-4 '-ethoxydiphenylmethane. The method comprises the following steps: using 5-bromo-2-chlorobenzoic acid as araw material to be acylated by thionyl chloride, and then carrying out acylation reaction with 1-nitro-4-(phenoxymethyl) benzene, reducing, acetylating, hydrogenating and ethylating to obtain the dapagliflozin intermediate 5-bromo-2-chloro-4'-ethoxydiphenylmethane. The method can effectively avoid the acylation reaction ortho-position by-product so that the preparation of dapagliflozin is convenient for quality control, the reaction is mild, the yield is high and the method has an industrial application prospect.
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Paragraph 0024-0027
(2020/04/06)
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- Preparation method of 5-bromo-2-chloro-4'-ethoxybenzophenone
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The invention discloses a preparation method of 5-bromo-2-chloro-4'-ethoxybenzophenone, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps:(1) carrying out direct reflux reaction on 5-bromo-2-chlorobenzoic acid and thionyl chloride in the absence of a solvent under the catalysis of DMF, and evaporating excessive thionyl chloride to obtain 5-bromo-2-chlorobenzoyl chloride after the reaction is finished; (2) adding dichloromethane into the material obtained in the step (1) for dissolving, directly adding silica gel loaded aluminum trichloride, performing reacting with phenethyl ether under a vacuum condition, performing filtering after the reaction is completed, washing the filtrate with a 5% sodium bicarbonate solution and water in sequence, performing evaporating to remove the solvent, and performing recrystallizing with a mixed solvent of ethanol and water to obtain 5-bromo-2-chloro-4'-ethoxybenzophenone. The method providedby the invention has the advantages of the small acid solvent generation amount, less difficult-to-treat wastewater, high product purity and yield, no generation of by-products, environmental protection, simple operation, and suitability for industrial production and popularization.
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Paragraph 0025-0026; 0028-0029; 0031-0032; 0034-0035; 0037
(2020/05/14)
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- GLUCOPYRANOSE DERIVATIVES USEFUL AS SGLT2 INHIBITORS
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The present invention is directed to glucopyranose derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT2 activity. More particularly, the compounds of the present invention are useful in the treatment of for example, Type II diabetes mellitus, Syndrome X, and complications and symptoms associated with said disorders.
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Page/Page column 53
(2020/06/10)
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- GLUCOPYRANOSE DERIVATIVES USEFUL AS SGLT2 INHIBITORS
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The present invention is directed to glucopyranose derivatives of formula (I), pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT2 activity. More particularly, the compounds of the present invention are useful in the treatment of for example, Type II diabetes mellitus, Syndrome X, and complications and symptoms associated with said disorders.
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Page/Page column 52-53
(2020/06/10)
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- Synthetic method for preparing empagliflozin intermediate
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The invention discloses a synthetic method for preparing an empagliflozin intermediate. The method comprises the following specific steps: 1) mixing a compound I with a solvent, preparing a compound II by using an acylation reagent, adding the compound II into a system of fluorobenzene and aluminum trichloride, carrying out a Friedel-Crafts reaction at room temperature, performing quenching with water, conducting liquid separation and washing successively, and concentrating an organic matter to obtain a compound III; 2) adding the compound III into a reaction kettle, adding a solvent, an alkali and a catalyst, then adding a compound IV, carrying out heating for a reaction, performing washing with water after the reaction, and conducting concentrating and crystallizing to obtain a solid compound V; and 3) adding the compound V into the reaction kettle, adding a solvent, an acid and a reducing agent, carrying out quenching with water after a reaction, conducting liquid separation and washing successively, concentrating an organic matter, and carrying out crystallizing to obtain a solid compound V. The method is simple and safe in process, high in product yield, easy in impurity control and suitable for industrial production.
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Paragraph 0050-0052; 0056-0057
(2020/07/02)
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- Preparation method of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane
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The invention relates to a preparation method of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane. The preparation method is characterized by comprising the following steps: step S1, preparation of 5-bromo-2-chlorobenzoyl chloride, step S2, preparation of 5-bromo-2-chloro-4'-ethoxybenzophenone, and step S3, preparation of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane. The invention further discloses the 5-bromine-2-chloro-4 '-ethoxydiphenylmethane prepared according to the preparation method of the 5-bromine-2-chloro-4'-ethoxydiphenylmethane. The invention further discloses the 5-bromine-2-chloro-4 '-ethoxydiphenylmethane prepared according to the preparation method of the 5-bromine-2-chloro-4'-ethoxydiphenylmethane. According to the preparation method of the 5-bromo-2-chloro-4 '-ethoxydiphenylmethane, traditional preparation process conditions are optimized and innovated, the method effectively improves the product purity, the reaction conversion rate and the production efficiency, has no special requirements on reaction conditions and equipment, is suitable for industrial production, causes less pollution to the environment and effectively realizes good combination of economic benefits, social benefits and ecological benefits.
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Paragraph 0034-0036; 0044-0060
(2020/09/23)
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- Preparation method of dapagliflozin impurity (by machine translation)
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The invention relates to a preparation method of dagliflozin impurity 5 - bromo -2 - chloro -2 ' - ethoxy benzophenone, which is sequentially subjected to chlorination, esterification, rearrangement and alkylation reaction to obtain a target product. The
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Paragraph 0034-0036; 0040-0042; 0046-0048
(2020/11/26)
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- Combined catalyst for use in specific Friedel-Crafts reactions
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The invention provides an application of a ferric trichloride and indium trichloride combined catalyst in a specific Friedel-Crafts reaction, more specifically, the invention provides an application of a ferric trichloride and indium trichloride combined Lewis acid catalyst in preparation of a key intermediate of empagliflozin, dapagliflozin and canagliflozin drugs. Compared with the prior art, the ferric trichloride and indium trichloride combined catalyst provided by the invention can greatly reduce the use of inorganic salt in the preparation process of the key intermediate of the empagliflozin, dapagliflozin and canagliflozin drugs, and obviously reduce the emission of waste water, waste gases and waste residues; and the ferric trichloride and indium trichloride combined catalyst can significantly improve the selectivity of para-position products in the preparation process of the key intermediate of the empagliflozin, dapagliflozin and canagliflozin drugs, can remarkably improve the quality and the yield of a target product, and remarkably reduce the process cost.
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Paragraph 0058-0059; 0063-0065; 0069-0070; 0074-0075
(2020/12/10)
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- Synthetic method for empagliflozin related substance IMPD
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The invention discloses a synthetic method for empagliflozin related substance IMPD. In a current synthetic method of IMPD, a whole synthetic route is longer and the total yield is lower. The synthetic method provided by the invention comprises the following steps: performing hydroxylation by using (2-chloro-5-iodophenyl)(4-fluorophenyl)methanone as a raw material to obtain (2-chloro-5-iodophenyl)(4-hydroxyphenyl)methanone, performing a reaction by using a carbonyl reducing agent to obtain 4-(5-iodo-2-chlorobenzyl)phenol, protecting phenolic hydroxyl groups by using protecting groups such as TBDMS, performing metallization of aromatic iodide by adopting a relatively stable and safe Grignard reagent i-PrMgCl.LiCl, performing methyl glucoside reduction by using a Lewis acid catalyst, and finally performing quenching to obtain the empagliflozin related substance IMPD. The synthetic method provided by the invention has the advantages of an abundant raw material source, a simple, quick andhigh-efficiency reaction, milder reaction conditions, a higher total yield and low costs.
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Paragraph 0079; 0080
(2019/07/10)
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- PROCESS FOR THE PREPARATION OF SOTAGLIFLOZIN
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Sotagliflozin may be prepared using schemes and intermediates disclosed herein. Sotagliflozin may be incorporated into pharmaceutical dosage forms for treatment of diabetes.
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Page/Page column 45; 46
(2019/09/18)
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- Deuterium modified C-glycoside derivatives of benzyl-4-chlorophenyl
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The invention belongs to the technical field of medicine, and in particular, relates to deuterium modified C-glycoside derivatives of benzyl-4-chlorophenyl or pharmaceutically acceptable salts thereof, a method for preparing the compounds, pharmaceutical
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Paragraph 0072; 0077-0079
(2019/12/25)
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- Reaches geleg net intermediate 5 - bromo -2 - chloride synthesis method (by machine translation)
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The invention reach gliclazide net intermediate 5 - bromo - 2 - chlorobenzene formyl chloride synthesis method, comprises the following steps: 1) the process for the manufacture of chlorine monoester A mixing with the solvent, adding catalyst, stirring an
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Paragraph 0031-0059
(2019/03/28)
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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 0511; 0513-0515; 0570; 0571; 0573; 0574
(2018/07/28)
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- Preparation method of Dapagliflozin isomer impurities I
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The invention discloses a preparation method of Dapagliflozin isomer impurities I. The preparation method comprises the following steps that a, 2-chlorine-5-bromobenzoic acid is dissolved in a first solvent; an acylation reagent is added; reaction is perf
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Paragraph 0012; 0032; 0033
(2018/08/03)
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- Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents
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The cardiovascular complications were highly prevalent in type 2 diabetes mellitus (T2DM), even at the early stage of T2DM or the state of intensive glycemic control. Therefore, there is an urgent need for the intervention of cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2 inhibitory effects and anti-platelet aggregation activities, and its anti-platelet effect mediated by NO was also confirmed in the presence of NO scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and excretion of urinary glucose during an oral glucose tolerance test in mice. Potent and multifunctional hybrid, such as compound 2, is expected as a potential candidate for the intervention of cardiovascular complications in T2DM.
- Li, Zheng,Xu, Xue,Deng, Liming,Liao, Ruoxian,Liang, Ruiying,Zhang, Bo,Zhang, Luyong
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p. 3947 - 3952
(2018/06/27)
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- 6-halogenated glucose C-glycoside as well as preparation method and application thereof
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The invention discloses a 6-halogenated glucose C-glycoside as well as a preparation method and application thereof. A structure of 6-halogenated glucose C-glycoside is shown in formula I; an intermediate can be synthesized efficiently with cheap and easily available raw materials; meanwhile, when the raw material is used for synthesizing Jardiance, dapagliflozin and the like, a reaction yield ishigh, and an obtained product has high purity and relatively high industrial application prospect.
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Paragraph 0072; 0073; 0074; 0079
(2018/11/03)
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- Amide Effects in C?H Activation: Noncovalent Interactions with L-Shaped Ligand for meta Borylation of Aromatic Amides
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A new concept for the meta-selective borylation of aromatic amides is described. It has been demonstrated that while esters gave para borylations, amides lead to meta borylations. For achieving high meta selectivity, an L-shaped bifunctional ligand has been employed and engages in an O???K noncovalent interaction with the oxygen atom of the moderately distorted amide carbonyl group. This interaction provides exceptional control for meta C?H activation/borylation.
- Bisht, Ranjana,Hoque, Md Emdadul,Chattopadhyay, Buddhadeb
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supporting information
p. 15762 - 15766
(2018/11/10)
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- Processes for the Preparation of SGLT-2 Inhibitors, Intermediates Thereof
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The present invention relates to novel, improved processes for the preparation of sodium glucose co-transporter 2 (SGLT-2) inhibitors and novel intermediates thereof. More particularly, the present invention relates to a novel, improved process for the preparation of gliflozin compounds such as empagliflozin and dapagliflozin, intermediates thereof. The product obtained from the processes of present invention may be amorphous or crystalline, or in the form of amorphous/crystalline solid dispersions/solutions with pharmaceutically acceptable polymers and preparation process thereof. Also, the products obtained from the present invention may be used for the preparation of medicaments for the prevention and/or treatment of diseases and conditions associated with SGLT-2 inhibition.
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Paragraph 0148
(2019/01/04)
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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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- Glucopyranosyl derivative and application thereof in medicine
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The invention relates to a glucopyranosyl derivative as a sodium-dependent glucose transporter (SGLT) inhibitor, a pharmaceutical composition containing the derivative and an application thereof in medicine, and in particular to the glucopyranosyl derivative as shown in a formula (I) or a pharmaceutically acceptable salt or all stereisomers thereof, or use of the pharmaceutical composition containing the derivative and the derivative and the pharmaceutical composition for preparing medicines treating diabetes and diabetes related diseases.
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Paragraph 0269; 0270; 0271
(2017/07/19)
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- SGLT-2 inhibitor intermediate synthesis method
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The invention discloses a SGLT-2 inhibitor intermediate synthesis method. The method utilizes a NaBH4-TMSCl complex reducing agent to reduce carbonyl into methylene. The synthesis method has the characteristics of less side reactions, good environmental friendliness, low price, use of easily available raw materials and large scale production feasibility.
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Paragraph 0013
(2017/08/27)
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- Novel method for synthesizing dapagliflozin intermediate compound
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The invention discloses a novel method for synthesizing a dapagliflozin intermediate compound. The method comprises the following steps: (1) by taking dichloromethane as a solvent and pyridine as a catalyst, reacting 5-bromo-2-chlorobenzoic acid and thionyl chloride to obtain 5-bromo-2-chlorobenzoyl chloride; (2) by taking dichloromethane as a solvent and solid acid as a catalyst, reacting phenetole and the 5-bromo-2-chlorobenzoyl chloride to obtain 5-bromo-2-chloro-4-ethoxydiphenylketone; and (3) by taking THF as a solvent, adding the 5-bromo-2-chloro-4-ethoxydiphenylketone concentrated solution obtained in the step (2); by taking acetic acid and aluminum trichloride as catalysts, adding sodium borohydride, and performing a reduction reaction; and after the reaction is completed, adding a saturated saline solution, and performing quenching at 25 DEG C or below to obtain 5-bromo-2-chloro-4-ethoxydiphenylmethane. The novel method disclosed by the invention has the advantages of cheap and available raw materials, simple and easy operation, no discharge of three wastes, high reaction yield and the like.
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Paragraph 0030-0031; 0034-0035; 0038-0039
(2018/04/01)
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- Preparation method of SGLT2 inhibitor intermediate
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The invention provides a preparation method of an SGLT2 inhibitor intermediate II. The preparation method includes that a compound V and an ethoxide reagent are subjected to nucleophilic substitution in a proper solution to obtain a compound II, wherein the compounding formula is shown as below, and X in the compound V structure is selected from Br or I. By the compounding route, the problem of purification difficulty caused by plenty of isomers in compounding routes in documentary reports is solved. Reaction operations are simple and convenient, the reagent is low in cost and easy to get, and the obtained product does not contain the isomers. The route is suitable for industrial production.
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Paragraph 0041
(2017/08/30)
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- ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF DAPAGLIFLOZIN
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Aspects of the present invention relates to an isolated intermediate of Dapagliflozin (Formula III) and its preparation, process for the preparation of Dapagliflozin, process for the preparation of crystalline propane-1,2,3-triol solvate of dapagliflozin, process for the preparation of L-proline complex of Dapagliflozin, solid premix of dapagliflozin with the polymer selected from the group consisting of eudragit, syloid, MCC Avicel PH 102 (1:1) and MCC Avicel PH 102 (1:2).
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Page/Page column 32; 33
(2017/03/28)
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- THE PRESENT INVENTION RELATES TO PROCESS FOR THE PREPARATION OF D-GLUCITOL, 1,5- ANHYDRO-1-C-[4-CHLORO-3-[[4-[[(3S)-TETRAHYDRO-3-FURANYL] OXY]PHENYL] METHYL]PHENYL]-, (1S) AND ITS CRYSTALLINE FORMS THEREOF.
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The present invention relates to process for the preparation of D-glucitol, 1,5- anhydro-l-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl] methyl]phenyl]-, (1S) formula- 1 and its crystalline forms thereof.
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Page/Page column 29
(2017/08/22)
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- PROCESSES FOR THE PREPARATION OF EMPAGLIFLOZIN
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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.
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Paragraph 0177; 0178
(2017/09/13)
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- Preparation method of Dapagliflozin intermediate used for treating II-type diabetes
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The invention discloses a preparation method of a Dapagliflozin intermediate used for treating II-type diabetes. The preparation method comprises the following steps: 1) performing a reaction on 5-bromine-2-chlorobenzoic acid and oxalyl chloride in anhydrous dichloromethane under the catalysis of DMF (dimethyl formamide), so as to obtain 5-bromine-2-chloro-benzoyl chloride; 2) under the condition that tert-Butyldimethylsilyl chloride exists, performing a reaction on 5-bromine-2-chloro-benzoyl chloride obtained in step 1) and phenetole under the catalysis of ferric trichloride, so as to obtain 5-bromine-2-chloro-4'-ethyoxyl benzophenone. According to the preparation method provided by the invention, no ortho-by-product is generated, and the yield of a target product is high, so that the good support of storage of raw materials is provided for Dapagliflozin. Additionally, the preparation method is mild in conditions and short in reaction time, therefore, the preparation method is suitable for industrial production and promotion.
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Paragraph 0028; 0034; 0038; 0042; 0046
(2017/10/10)
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- Antidiabetic compound and preparation method and application thereof
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The invention discloses an antidiabetic compound and a preparation method and application thereof, and belongs to the technical field of medicine. The chemical structure of the compound is shown as a formula (I) (please see the formula in the description), wherein R is selected from i-Pr, Cl and COCH2Cl. According to the antidiabetic compound and the preparation method and application thereof, 2-chloro-5-bromobenzoic acid and D-gluconolactone are taken as starting raw materials, and three Dapagliflozin derivatives are finally obtained through reacting; the optimal reaction condition of different positioning groups is determined according to the reaction conditions of a Friede-Crafts alkylation reaction of the different positioning groups; in addition, a novel stereoisomerism splitting method is applied, therefore, the reaction conditions are optimized, the reaction cost is greatly lowered, the yield is increased, the used raw materials are cheap and easy to obtain, and the wide applicability is achieved.
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Paragraph 0055; 0056; 0057
(2017/09/19)
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- Glucopyranosyl derivative and application thereof in medicines
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The invention relates to a glucopyranosyl derivative used as a sodium-dependent glucose transporter (SGLT) inhibitor, a medicinal composition containing the derivative, and an application of the derivative and the medicinal composition in medicines, and especially relates to the glucopyranosyl derivative represented by formula (I) or a pharmaceutically acceptable salt or all stereoisomers thereof, or the medicinal composition containing the derivative, and a use of the derivative and the medicinal composition in the preparation of medicines for treating diabetes and diabetes related diseases.
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Paragraph 0446; 0448; 0449; 0450
(2016/10/08)
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- PROCESS FOR PREPARATION OF DAPAGLIFLOZIN
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The present invention relates to a process for the preparation of amorphous dapagliflozin. The present invention relates to 2,3-butanediol solvate of dapagliflozin and process for its preparation.
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Paragraph 0188
(2016/11/21)
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- C - aryl glucoside SGLT2 inhibitor
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The invention relates to the field of medicines related to diabetes mellitus and particularly relates to a 2-type sodium-glucose co-transporter (SGLT2) inhibitor with a multi-aryl glucoside structure and shown as the specification, a preparation method thereof, a medicine composition taking the compound as an active components and an application thereof in preparing medicines for resisting diabetes mellitus.
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Paragraph 0229
(2017/04/28)
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- GLUCOPYRANOSYL DERIVATIVES AND THEIR USES IN MEDICINE
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Disclosed are glucopyranosyl derivatives used as sodium dependent glucose cotransporters (SGLTs) inhibitors, intermediates or preparation processes thereof, and pharmaceutical uses thereof, especially glucopyranosyl derivatives represented by Formula (I), or pharmaceutically acceptable salts or all stereoisomers thereof, pharmaceutical compositions containing these derivatives and their uses for treatment of diabetes and diabetes-related diseases.
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Paragraph 00227
(2015/04/15)
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- Regioselective synthesis of 1-substituted indazole-3-carboxylic acids
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In this article, we study the synthesis of 1-substituted indazole-3-carboxylic acids from 2-halobenzoic acids.
- Veerareddy, Arava,Gogireddy, Surendrareddy,Dubey
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p. 1311 - 1321
(2015/04/27)
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- PROCESS FOR THE PREPARATION OF EMPAGLIFLOZIN
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An improved process for the preparation of empagliflozin is disclosed. Novel intermediates of formulas (13) and (14) for the preparation of empagliflozin are also disclosed, wherein R1 and R2 are independently hydrogen or hydroxyl protecting groups.
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Page/Page column 14; 15
(2015/07/16)
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- OPTICALLY PURE BENZYL-4-CHLOROPHENYL-C-GLUCOSIDE DERIVATIVE
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The present invention belongs to the field of pharmaceutical technology, more specifically relates to optically pure benzyl-4-chlorophenyl-C-glucoside derivatives represented by formulae (II) and (III), a process for preparing these compounds and intermediates thereof, a pharmaceutical formulation and a pharmaceutical composition containing these compounds, and the use of the optically pure benzyl-4-chlorophenyl-C-glucoside derivative as a sodium glucose co-transporter (SGLT) inhibitor in manufacture of a medicament for treating and/or preventing diabetes mellitus (including insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus) or diabetes-associated diseases (including insulin resistance disease and obesity)
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Paragraph 0068
(2015/07/15)
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- Optically pure benzyl-4-chlorophenyl-C-glucoside derivatives as SGLT inhibitors (diabetes mellitus)
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The present invention belongs to the field of pharmaceutical technology, more specifically relates to optically pure benzyl-4-chlorophenyl-C-glucoside derivatives represented by formulae (II) and (III), a process for preparing these compounds and intermediates thereof, a pharmaceutical formulation and a pharmaceutical composition containing these compounds, and the use of the optically pure benzyl-4-chlorophenyl-C-glucoside derivative as a sodium glucose co-transporter (SGLT) inhibitor in manufacture of a medicament for treating and/or preventing diabetes mellitus (including insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus) or diabetes-associated diseases (including insulin resistance disease and obesity) or
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Paragraph 0037; 0038
(2015/07/15)
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- OPTICALLY PURE BENZYL-4-CHLOROPHENYL-C-GLUCOSIDE DERIVATIVE
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The present invention relates to a pharmaceutical technology, and more specifically, to optically pure benzyl-4-chloro-phenyl glucoside derivatives represented by the chemical formula II and III or a pharmaceutically acceptable salt thereof. The present invention also relates to a method for preparing the compounds and intermediates thereof, pharmaceutical formulations and pharmaceutical compositions containing the compounds, and the use of the optically pure benzyl-4-chloro-phenyl glucoside derivatives as sodium glucose co-transporter (SGLT) inhibitors for the prevention and treatment of the diabetes including the insulin dependent diabetes mellitus and non-insulin dependent diabetes mellitus and the diabetes-related deseases such as insulin-resistant diseases and obesity.COPYRIGHT KIPO 2015
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Paragraph 0143-0145
(2016/11/24)
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- Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes
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SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were found to have a slightly longer tmax and half-life (t 1/2), dose-dependent increase in urinary glucose excretion (UGE) in rats, and slightly superior effects on UGE in dogs while retaining similar in vitro inhibitory activities against hSGLT2. In particular, deuterated compound 41 has the potential to be a robust long-acting antidiabetic agent.
- Xu, Ge,Lv, Binhua,Roberge, Jacques Y.,Xu, Baihua,Du, Jiyan,Dong, Jiajia,Chen, Yuanwei,Peng, Kun,Zhang, Lili,Tang, Xinxing,Feng, Yan,Xu, Min,Fu, Wei,Zhang, Wenbin,Zhu, Liangcheng,Deng, Zhongping,Sheng, Zelin,Welihinda, Ajith,Sun, Xun
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p. 1236 - 1251
(2014/03/21)
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- Inhibitor of Sodium-Dependent Glucose Transport Protein and Preparation Method Therefor and Use Thereof
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Disclosed is a compound of formula I, or a pharmaceutically acceptable salt, solvate, polymorph, enantiomer or racemic mixture thereof, wherein R1 and R2 are each independently hydrogen, —OH, alkyl, —CF3, —OCHF2, —OCF3 or halogen; R3 is cycloalkyl, —OCH2CF3, —OCH2CHF2, —OCH2CH2F or —OCH2CH3; R4 is hydrogen, —OH, —O aryl, —OCH2 aryl, alkyl, cycloalkyl, —CF3, —OCHF2, —OCF3, —OCH2CF3, —OCH2CHF2, —OCH2CH2F or halogen; A is —CX1X2, wherein X1 and X2 are each independently H, F and Cl, and when both X1 and X2 are H, R3 is not —OCH2CH3. The compound has an activity of inhibitors of sodium-dependent glucose transport protein. Also disclosed is a method for preparing the compound, a pharmaceutical composition comprising the compound, use of the compound and pharmaceutical composition thereof in preparing medicaments of SGLT2 inhibitors and treating related diseases.
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Paragraph 0072; 0073
(2014/03/24)
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- C-GLYCOSIDE DERIVATIVES
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The present invention involves a compound represented by general formula (I), a derivative thereof and a use thereof: wherein R1, R2, R3, R4, R5a, R5b, R5c and X are defined as in the description.
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Paragraph 0098; 0099
(2014/05/20)
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- C-GLYCOSIDE DERIVATIVES
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The present invention involves a compound represented by general formula (I), a derivative thereof and a use thereof: wherein R1, R2, R3, R4, R5a, R5b, R5c and X are defined as in the description.
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Paragraph 0080-0081
(2014/05/20)
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- Design, synthesis and biological evaluation of 5-amino-1H-pyrazole-4- carboxamide derivatives as potential antitumor agents
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Adenosine deaminase (ADA) inhibitors have been found to have antitumor activities. Here, thirteen potential adenosine deaminase inhibitors 5-amino-1H-pyrazole-4-carboxamide derivatives were designed, synthesized and screened for antitumor activities. Comp
- Yang, Baowei,Liu, Wukun,Mei, Yicheng,Huang, Dandan,Qian, Hai,Huang, Wenlong,Gust, Ronald
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p. 749 - 755
(2014/07/07)
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- Substituted benzamides with activity towards EP4 receptors
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The present invention belongs to the field of EP4 receptor ligands. More specifically it refers to compounds of general formula (I) having great affinity and selectivity for the EP4 receptor. The invention also refers to the process for their preparation, to their use as medicament for the treatment and/or prophylaxis of diseases or disorders mediated by the EP4 receptor as well as to pharmaceutical compositions comprising them.
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Paragraph 0104
(2014/08/20)
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- SUBSTITUTED BENZAMIDES WITH ACTIVITY TOWARDS EP4 RECEPTORS
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The present invention belongs to the field of EP4 receptor ligands. More specifically it refers to compounds of general formula (I) having great affinity and selectivity for the EP4 receptor. The invention also refers to the process for their preparation, to their use as medicament for the treatment and/or prophylaxis of diseases or disorders mediated by the EP4 receptor as well as to pharmaceutical compositions comprising them.
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Page/Page column 38
(2014/08/20)
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- Efficient synthesis of empagliflozin, an inhibitor of SGLT-2, utilizing an AlCl3-promoted silane reduction of a β-glycopyranoside
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An efficient production synthesis of the SGLT-2 inhibitor Empagliflozin (5) from acid 1 is described. The key tactical stage involves I/Mg exchange of aryl iodide 2 followed by addition to glucono lactone 3 in THF. Subsequent in situ treatment of the resulting lactol with HCl in MeOH produces β-anomeric methyl glycopyranoside 4 which is, without isolation, directly reduced with Et3SiH mediated by AlCl3 as a Lewis acid in CH 2Cl2/MeCN to afford 5 in 50% overall yield. The process was implemented for production on a metric ton scale for commercial launch.
- Wang, Xiao-Jun,Zhang, Li,Byrne, Denis,Nummy, Larry,Weber, Dirk,Krishnamurthy, Dhileep,Yee, Nathan,Senanayake, Chris H.
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supporting information
p. 4090 - 4093
(2014/10/15)
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- STROBILURIN TYPE COMPOUNDS FOR COMBATING PHYTOPATHOGENIC FUNGI
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The present invention relates to novel strobilurine type compounds I, processes for preparing these compounds, a use of compounds of the formula I and/or their agriculturally useful salts for controlling phytopathogenic fungi, to compositions comprising at least one such compound, to plant health applications, and to seeds coated with at least one such compound.
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Page/Page column 101
(2015/01/07)
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- C-ARYL GLUCOSIDE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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C-aryl glucoside derivatives, preparation processes and pharmaceutical uses thereof are disclosed. In particular, C-aryl glucoside derivatives represented by formula (I), with each substituent defined in the application, pharmaceutically acceptable salts or stereoisomers thereof, their preparation methods, and pharmaceutical compositions containing the derivatives as well as their uses as therapeutic agents, particularly as sodium-dependent glucose cotransporter (SGLT)-1 inhibitors, are disclosed.
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Paragraph 0225
(2013/06/04)
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