cas 161798-03-4, ETHYL 2-(3-FORMYL-4-ISOBUTOXYPHENYL)-4-METHYLTHIAZOLE-5-CARBOXYLATE

Articles about 161798-03-4Total 19 be found

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Controlled Relay Process to Access N-Centered Radicals for Catalyst-free Amidation of Aldehydes under Visible Light
Nitrogen-centered radicals have attracted increasing attention as a versatile reactive intermediate for diverse C–N bond constructions. Despite the significant advances achieved in this realm, the controllable formation of such species under catalyst-free conditions remains highly challenging. Here, we report a new relay process involving the slow in situ generation of a photoactive N-chloro species via C–N bond formation, which subsequently enables mild and selective access to N-centered radicals under visible light conditions. The utility of this approach is demonstrated by the conversion of aldehydes to amides, employing N-chloro-N-sodio carbamates as a practical amidating source. This synthetic operation obviates the need for catalysts, external oxidants, and coupling reagents that are typically required in related processes, consequently allowing high functional group tolerance and excellent applicability for late-stage functionalization. Amides are an important class of structural motifs prevalently found in bioactive compounds and synthetic materials of great significance. Amidation of aldehydes has been established as an atom-efficient strategy for amide synthesis; however, current methods lack in applicability mainly due to the requirement of troublesome reagents. In this article, we describe an unconventional relay process to convert aldehydes to amides under catalyst-, oxidant-, and coupling-reagent-free conditions, which is enabled by the development of a new mechanistic platform that gives efficient and controllable access to N-centered radicals under visible light. A wide range of (hetero)aromatic and aliphatic aldehydes can be employed, including those derived from biologically relevant complex molecules. We anticipate that the accomplished methodological advances, combined with the unique mechanistic features, will lead to the widespread application of the present strategy in broad research fields. A catalyst-free approach for controlled access to N-centered radicals is described, which enables the conversion of aldehydes to amides via an unconventional relay process harnessing visible light. The key tactic relies on the use of photostable N-chloro-N-sodio-carbamate amidating reagent that leads to slow incorporations of a photoactive radical source via C–N formation and other involved intermediates thereafter. This methodology displays excellent applicability and sustainable chemistry credentials and, thus, holds a promise for finding broad applications.
Chang, Sukbok,Jeon, Hyun Ji,Jung, Hoimin,Kim, Dongwook,Lee, Wongyu,Seo, Sangwon
supporting information
p. 495 - 508
(2021/01/28)

Design, synthesis, cytotoxic evaluation and molecular docking studies of novel thiazolyl α-aminophosphonates
Abstract: A new class of thiazolyl α-aminophosphonate derivatives was synthesized by one-pot Kabachnik–Fields reaction of ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate with various aryl amines and diethyl phosphite under solvent-free conditions using β-cyclodextrin supported sulfonic acid (β-CD-SO3H) as an efficient, reusable and heterogeneous solid acid catalyst. The products were obtained in good to excellent yields at shorter reaction time. All the title compounds were screened for cytotoxic activity against human breast cancer (MCF-7 and MDA-MB-231), prostate cancer (DU-145) liver cancer (HepG2) and HeLa cancer cell lines using sulfarodamine-B (SRB assay). Compounds (8b, –4OMe), (8h, –4NO2) and (8j, –2I, –4CF3) showed better anticancer activity when compared with standard drug Adriamycin. Further in-silico target hunting reveals the anticancer activity of the designed compounds by inhibiting DNA topoisomerase II. Graphical abstract: [Figure not available: see fulltext.].
Gundluru, Mohan,Badavath, Vishnu Nayak,Shaik, Haroon Yasmin,Sudileti, Murali,Nemallapudi, Bakthavatchala Reddy,Gundala, Sravya,Zyryanov, Grigory V.,Cirandur, Suresh Reddy
p. 1139 - 1160
(2020/11/16)

New preparation method of febuxostat intermediate
The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.
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Paragraph 0111-0116

(2020/03/06)

Method for synthesizing febuxostat and intermediate thereof
The invention relates to a method for synthesizing febuxostat and an intermediate thereof, specifically a method for synthesizing 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The method comprises the following steps: preparing 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate; enabling the product obtained in the step (a) to react in DMF (Dimethyl Formamide) in the presence of potassium carbonate and bromo-isobutane, adding water and ethyl acetate for extraction, concentrating to obtain an organic layer, and recrystallizing with DMF to obtain 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The invention also relates to 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester and 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazoleethyl formate and application thereof to the preparation of febuxostat. The method of the invention has excellent performance.
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Paragraph 0187-0190; 0197-0204

(2020/05/02)

Febuxostat and intermediates and synthesis thereof
The invention relates to febuxostat and intermediates and synthesis thereof, in particular to a method for synthesizing 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate, which comprisesthe following operation steps: (1) adding a reactant 2-(4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate into a mixture of polyphosphoric acid and methanesulfonic acid, and uniformly stirring the materials; (2) adding a Darf reaction reagent hexamethylenetetramine into the reaction mixture while stirring, continuously reacting, and cooling; and (3) adding saturated brine ice, separating out solid, filtering, cleaning the solid with water to-be-neutral, and drying to obtain the product. The invention also relates to 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate and to the usethereof for the preparation of febuxostat. The method has excellent performance.
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Paragraph 0159-0162

(2020/05/09)

Synthesis, molecular docking, DFT study of novel N-benzyl-2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamide derivatives and their antibacterial activity
A series of febuxostat based new chemical entities was synthesized using microwave method and characterized by NMR, mass and FT-IR spectral studies. Molecular docking of febuxostat amide nucleus substitution compounds 8c (-7.91kcal/mol), 8g (-7.94 kcal/mol) exhibiting high binding energy against ALK receptors. Theoretical investigation of MEPs, HOMO, LUMO and energy gap of HOMO-LUMO were calculated by B3LYP/6-31G method. Among the tested compounds, methoxy substituted compound 8g showed highest antibacterial activity against S. aereus and B. subtilis.
Sam Daniel Prabu,Lakshmanan, Sivalingam,Thirumurugan,Ramalakshmi,Arul Antony
p. 619 - 626
(2020/02/06)

Method for continuously preparing febuxostat
The invention discloses a method for continuously preparing febuxostat. The method comprises the following steps: by taking a compound represented by a formula (II) as a raw material, carrying out anetherification reaction to obtain a compound solution represented by a formula (III), filtering, carrying out reduced pressure distillation on filtrate to recover excessive bromo-iso-butane, carryingout a cyanation reaction on the residual filtrate to obtain a compound solution represented by a formula (IV), adding an alkali, and carrying out an ester hydrolysis reaction to obtain the febuxostat(I). By optimizing the preparation process of febuxostat, the whole preparation of the febuxostat can be continuously produced, the prepared febuxostat is high in yield and good in purity, the use ofa large amount of acid solvents in the traditional process is avoided, the operation steps are simple, and the preparation method is particularly suitable for industrial production.
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Paragraph 0009; 0014; 0017

(2020/07/06)

Synthesis method of febuxostat impurity
The invention provides a synthesis method of a febuxostat impurity, which is characterized in that 2-[3-formyl-4-isobutoxyphenyl]-4-methylthiazole-5-formic acid is used as a raw material, and the febuxostat impurity is prepared by a four-step synthesis method. The synthesis process provided by the invention has the advantages of mild reaction conditions, no need of special chemical reagents, highyield and purity up to 99%, and can be used as a standard substance or a reference substance for quality control of febuxostat series products.
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Paragraph 0093-0095

(2020/07/13)

High purity febuxostat preparation method
The invention relates to febuxostat preparation method, wherein the 2 - (3 - thiophene - 4 - hydroxy-phenyl) - 4 - methyl thiazole - 5 - carboxylic acid ethyl ester with isobutyl bromide after completion of the reaction, the reaction solution after treatment as follows: 1) adding purified water, separating out the first crystal; 2) a first crystal to purified water beating, get the secondary crystal; 3) the secondary crystal to 1: 1.2 - 2.0 mass ratio of ethanol - formic acid solution recrystallization, to obtain compound (2 - (3 - formyl - 4 - isobuoxy - phenyl) - 4 - methyl - thiazole - 5 - carboxylic acid ethyl ester (FBT - 1). Through the step of optimizing the reaction post, obviously improves the key intermediate purity and yield, thereby improving the purity of the final product febuxostat and yield.
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Paragraph 0006; 0028-0037

(2019/07/04)

Preparation method of Febuxostat
The invention provides a preparation method of Febuxostat, and belongs to the technical field of pharmaceutical synthesis. According to the method provided by the invention, with 2-(3-formyl-4-hydroxyphenyl)-4-methyl-thiazole-5-ethyl carboxylate as a raw material, the Febuxostat is synthesized through an isobutylation reaction, a cyanation reaction and a hydrolysis reaction. The synthesis route issimple; through aftertreatment of the product of each step of the reaction as well as refining for purification, crystal regulation and the like on crude products, the product purity and yield are remarkably improved, the cost is lowered, and the operation is easier and more reasonable; moreover, the preparation method provided by the invention has the advantages of mild reaction conditions and lower energy consumption and is more suitable for industrial production.
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Paragraph 0069-0072; 0080; 0081

(2019/02/25)

New preparation method of febuxostat
Belonging to the technical field of pharmaceutical synthesis, the invention in particular relates to a preparation method of a febuxostat intermediate I, a preparation method of a febuxostat intermediate II and application thereof, as well as a preparation method of a febuxostat product. The preparation method of the febuxostat product includes: preparing the febuxostat intermediate I and the febuxostat intermediate II, directly adding water and organic alkali into a solution of the febuxostat intermediate II, and carrying out hydrolysis reaction; at the end of the reaction, adjusting the pH to 6.0-7.0 with hydrochloric acid, adding water for crystallization, performing cooling and centrifugation to obtain a febuxostat crude product, and then performing further preparation to obtain the febuxostat product. The febuxostat finished product has high purity, the preparation method has high yield and is low in cost, solid-liquid separation is easy to realize, the residual solvent is easilyremoved in the finished product preparation step, and the method is convenient for "consistency evaluation" by a preparation manufacturer, has great market competition advantage, and is green and environmentally friendly.
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Paragraph 0066-0068; 0071-0073; 0076-0078

(2019/10/01)

Synthesis method of Febuxostat isomeride
The invention relates to a synthesis method of Febuxostat isomeride. The method comprises the following steps: firstly ensuring that 2-(3-aldehyde-4- hydroxyphenyl)-4-methylthiazole-5-nonanoic acid-ethyl ester (a compound 1) taken as a raw material and bromobutane are reacted, so as to obtain a compound 2, secondly, performing oximation and dehydration on the compound 2, so as to obtain a cyan compound 3, and thirdly, performing hydrolysis on the compound 3, so as to obtain a compound 4.
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Paragraph 0024

(2018/08/04)

2 - (3 - aldehyde - 4 - isobuoxy phenyl) - 4 - methyl thiazole - 5 - carboxylic acid ethyl ester
The invention provides a method for synthesizing high-purity ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate. The method comprises the following steps of carrying out thioacylation reaction on p-cyanophenol and thioacetamide as starting materials to obtain 4-hydroxythiobenzamide (II), directly carrying out thiazole reaction on the reaction product which is not separated and separating to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazole formate (III); carrying out formylation reaction on the compound as shown in the formula (III) to obtain ethyl 2-(3-carbaldehyde-4-hydroxyphenyl)-4-methyl-5-thiazole formate (IV), directly carrying out isobutylation reaction on the reaction product which is not separated to obtain ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate (I) of which the purity is equal to or greater than 99% and the content is equal to or greater than 99%. The production process is optimized and thus the quality of the product is greatly improved and the high yield is achieved.
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Paragraph 0054-0059

(2017/08/25)

Compound 2 - (3-aldehyde group-4-isobuoxy phenyl) - 4-methyl-thiazole-5-carboxylic acid ethyl ester and non-cloth rope Tanzania method for the preparation of
The invention provides a preparation method of 2-(3-formyl-4-isobutoxy phenyl)-4-methyl thiazole-5-ethyl formate which is obtained by using 4-isobutoxy cyanophenyl as an initial raw material and through a series of reactions. The invention also provides a preparation method of febuxostat, which comprises the following steps: reacting 2-(3-formyl-4-isobutoxy phenyl)-4-methyl thiazole-5-ethyl formate with hydroxylamine hydrochloride under the action of a catalyst to obtain a compound with a structure as shown in formula (VIII); hydrolyzing the compound with the structure as shown in formula (VIII) under an alkaline condition, and performing acidification to obtain febuxostat. The preparation method of the invention prepares febuxostat without using cyanides, and is high in safety. The preparation methods of the invention are simple in operation and high in yield. Experiment results show that the yield of step (A) is up to 90%, the yield of step (B) is up to 85%, the yield of step (C) is up to 90%, the yield of step (D) is up to 90%, and the yield of step (E) is up to 97%.
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(2016/10/09)

A NOVEL PROCESS FOR THE PREPARATION OF FEBUXOSTAT
The present invention relates to a novel preparation method for 2-(3-cyano-4-isobutoxyphenyl)- 4-methyl-1,3-thiazole-5-carboxylic acid (Febuxostat) via novel and high yielded conversion of a formyl group in to a cyano group.
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Page/Page column 12

(2015/02/25)

AN IMPROVED PROCESS FOR PREPARATION OF FEBUXOSTAT AND ITS POLYMORPHIC CRYSTALLINE FORM C THEREOF
The present invention relates to process of preparation of 2-(3-cyano-4- isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid (Febuxostat). The present invention in particular relates to an efficient and easily to operate scalable process of manufacturing of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid (Febuxostat) of Formula I and its crystalline polymorphic Form C.
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Page/Page column 15; 21; 23

(2012/10/18)

PROCESS FOR FEBUXOSTAT
The present invention provides a process for the preparation of 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester. The present invention also provides a process for the preparation of 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester. The present invention further provides novel crystalline Forms of febuxostat, processes for their preparation and pharmaceutical compositions comprising them. The present invention further provides febuxostat crystalline particles having a mean particle size of less than about 25 μm, the methods for the manufacture of said crystalline particles, and pharmaceutical compositions comprising said crystalline particles.
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Page/Page column 11

(2013/02/27)

PROCESSES FOR PREPARING FEBUXOSTAT
Febuxostat can be prepared from the compound of the following formula (VI); Formula (VI) has been prepared in a one-pot process by combining a compound of the following formula (II); with an organic solvent, isobutyl halide and an inorganic base, to obtain a compound of the following formula (III); Formula III is optionally filtered before combining it with hydroxylamine base or hydroxylamine HCl. A water scavenger is added to obtain the compound of formula VI. Febuxostat can then be prepared, for example, by combining the compound of formula VI with one organic solvent and an alkali metal hydroxide.
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Page/Page column 15

(2011/04/18)

PROCESS FOR THE PREPARATION OF 2-[3-CYANO-4-(2-METHYLPROPOXY)PHENYL]-4-METHYLTHIAZOLE-5-CARBOXYLIC ACID AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
The present invention relates to novel and improved processes for the preparation of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid compound of formula-1 and its pharmaceutically acceptable salts thereof. the present invention also provides the novel process for the preparation of crystalline forms of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid compound of formula-1 and its intermediates.
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Page/Page column 46

(2011/12/02)