- BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS
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The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na+- K+- 2CI- - cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.
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Page/Page column 167-168
(2019/10/30)
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- Method for synthesizing 5-chlorothiophene-2-formic acid with thiophene-2-formic acid as raw material
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The invention discloses a method for synthesizing 5-chlorothiophene-2-formic acid with thiophene-2-formic acid as a raw material. According to the method, the thiophene-2-formic acid is taken as a substrate, trichloroisocyanuric acid is taken as a chlorinating agent, and under an acidic condition, a substitution reaction is carried out to generate the 5-chlorothiophene-2-formic acid. The method isconcise, the operation is simple, the product is high in yield, industrial production is facilitated, raw materials are cheap, and the 5-chlorothiophene-2-formic acid has a wide use range and very high production application value.
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Paragraph 0027; 0031-0036
(2019/10/22)
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- Low cost preparation method of high purity 5-chlorothiophene-2-formyl chloride
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The invention relates to a low cost preparation method of high purity 5-chlorothiophene-2-formyl chloride. According to the preparation method, 2-chlorothiophene and a formylation reagent carry out reactions to generate 5-chlorothiophene-2-formaldehyde, then 5-chlorothiophene-2-formaldehyde is oxidized by an oxidant to generate 5-chlorothiophene-2-formic acid, and finally 5-chlorothiophene-2-formic acid and an acyl-chlorination reagent carry out acyl-chlorination reactions to generate 5-chlorothiophene-2-formyl chloride. 5-chlorothiophene-2-formyl chloride can be used as a key intermediate inrivaroxaban preparation. The preparation method has the advantages of cheap and easily-available raw materials, simple technical route, low raw material cost, little discharge amount of wastewater, low salt content of wastewater, environmental friendliness, and high reaction selectivity. The purity of obtained 5-chlorothiophene-2-formyl chloride is high, and the industrial production of high purity rivaroxaban is promoted.
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Paragraph 0056-0062
(2019/03/26)
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- Method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis
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The invention relates to a method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis. The method comprises the following steps: leading or adding a chlorinated reagent into 2-thiophenecarboxaldehyde for heat insulation reaction, so as to obtain an intermediate 5-chlorine2-thiophenecarboxaldehyde after the reaction is completed, wherein the intermediate 5-chlorine2-thiophenecarboxaldehyde is directly used for the next reaction without separation; slowly dropping the intermediate 5-chlorine2-thiophenecarboxaldehyde into pre-cooled caustic soda liquid, controlling the reaction temperature to be not higher than 30 DEG C, cooling after the dropping is completed, slowly leading chlorine into the pre-cooled caustic soda liquid for heat insulation reaction after the leading of the chlorine is completed, cooling to 5 DEG C after a center control reaction is completed, adding sodium sulfite for quenching, adding a solvent for extraction and impurities elimination, regulating the pH value of a water phase with concentrated hydrochloric acid, performing suction filtration, recrystallizing a filter cake, and drying, so as to obtain an target compound. According to the method, the defects of the prior art of being high in raw materials, complex in operation and more in three wastes are overcome; the provided method for synthesizing 5-chlorothiophene-2-carboxylic acidis suitable for industrial production.
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Paragraph 0027; 0029; 0030; 0032
(2018/12/13)
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- A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
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Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
- Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
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supporting information
p. 3931 - 3943
(2018/09/11)
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- Synthetic method of 5-chloro-2-thiophenecarboxylic acid
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The invention discloses a synthetic method of 5-chloro-2-thiophenecarboxylic acid. 2-bromo-5-chlorothiophene reacts with magnesium to generate a Grignard reagent of 5-chloro-2-thienylmagnesium bromide, and then the 5-chloro-2-thienylmagnesium bromide reacts with dry ice and is hydrolyzed under the acid condition to generate the 5-chloro-2-thiophenecarboxylic acid. The synthetic method is simple, and the yield and purity of the product are high. The reaction equation is shown in the figure.
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Paragraph 0011; 0031; 0032; 0033
(2017/08/28)
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- A 5 - chlorine thiophen - 2 - carboxylic acid
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The invention relates to the technical field of preparation of heterocyclic compounds, and particularly discloses a preparation method of 5-chlorothienyl-2-carboxylic acid. The preparation method comprises the following steps: dissolving the raw material 5-chloro-2-acetylthiophene in acetone, dropwisely adding a potassium dihydrogen phosphate water solution at 0-10 DEG C during reaction, dropwisely adding a sodium chlorite water solution during reaction, and oxidizing at 20-30 DEG C to obtain the 5-chlorothienyl-2-carboxylic acid. The method has the advantages of mild operating conditions, high controllability, short reaction steps, high yield and no pollution, and is suitable for industrial production.
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Paragraph 0024-0041
(2017/08/26)
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- 5-chlorothiophene-2-carbonylchloride intermediate and preparation method thereof
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The invention discloses a 5-chlorothiophene-2-carbonylchloride intermediate and a preparation method thereof. The preparation method comprises the following step that a compound 3 is subjected to a hydrolysis reaction shown as follows (please see the hydrolysis reaction in the description). According to the preparation method, the process is safe and simple, aftertreatment is convenient, both an intermediate product and a final product are easy to purify, the purity and the yield are high, the production cost is low, and industrialized production is easy to achieve.
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Paragraph 0059; 0060; 0061
(2016/12/22)
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- Copper-catalyzed synthesis of aromatic carboxylic acids from arylboronic acids and acetyl acetate
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A simple and efficient copper-catalyzed method for the synthesis of aromatic carboxylic acids in moderate to high yields with great functional-group compatibility in the substrates has been developed. The new method uses readily available arylboronic acids and acetyl acetate as the starting materials and inexpensive CuI as the catalyst.
- Zheng, Rui,Zhou, Qizhong,Gu, Haining,Jiang, Huajiang,Wu, Jiashou,Jin, Zhengneng,Han, Deman,Dai, Guoliang,Chen, Rener
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supporting information
p. 5671 - 5675
(2014/12/11)
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- Flash carboxylation: Fast lithiation-carboxylation sequence at room temperature in continuous flow
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A method for the direct lithiation of terminal alkynes and heterocycles with subsequent carboxylation in a continuous flow format was developed. This method provides carboxylic acids at ambient conditions within less than five seconds with only little excess of the organometallic base and CO2. This journal is the Partner Organisations 2014.
- Pieber, Bartholomaeus,Glasnov, Toma,Kappe
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p. 13430 - 13433
(2014/04/03)
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- METHOD FOR CARBOXYLIZING AROMATES AND HETETOAROMATES USING CO2
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The present invention relates to a process for the preparation of aromatic and heteroaromatic carboxylic acids using CO2.
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Page/Page column 3
(2013/02/27)
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- CORTICOID-17,21-DICARBOXYLIC ESTERS AND CORTICOSTEROID 17-CARBOXYLIC ESTER 21-CARBONIC ESTERS, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICALS CONTAINING THESE COMPOUNDS
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Corticoid 17,21-dicarboxylic esters and corticosteroid 17-carboxylic ester 21-carbonic esters, processes for their preparation and pharmaceuticals containing these compounds Corticoid 17,21-dicarboxylic esters and corticoid 17-carboxylic ester 21-carbonic esters of the formula I are described, in which A is CHOH and CHCl, CH2, C═O or 9(11) double bond; Y is H, F or Cl; Z is H, F or methyl; R(1) is aryl or hetaryl; R(2) is alkyl and R(3) is H or methyl. They are obtained, inter alia, by reacting a compound of the formula II, in which R(5) is OH, with an activated carboxylic acid of the formula III, R(6)—CO—(O)n[(C1-C4)-alkyl]m-R(1) ??III. They have a very strong local and topical antiinflammatory action and exhibit a very good ratio of local to systemic antiinflammatory effects. They are used, inter alia, as agents for treating inflammatory dermatoses.
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- Synthesis and antitumour activity of new derivatives of flavone-8- acetic acid (FAA). Part 31): 2-Heteroaryl derivatives
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A range of 14 derivatives of flavone-8-acetic acid (FAA) with a heterocyclic substituent in place of the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. Some of the compounds, notably 2c,d and s, showed significant in vivo activity and these require further studies in order to evaluate their potential for development.
- Aitken, R. Alan,Bibby, Michael C.,Bielefeldt, Florian,Double, John A.,Laws, Andrea L.,Mathieu, Anne-Laure,Ritchie, Robert B.,Wilson, David W. J.
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p. 405 - 411
(2007/10/03)
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- Corticosteroid 17-alkyl carbonate 21-[0]-carboxylic and carbonic esters, and pharmaceuticals containing these compounds
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Corticoid 17-alkyl carbonate 21-carboxylic and carbonic esters of the formula I STR1 are described in which A is CHOH and CHCl, CH2, C=O or 9(11) double bond; Y is H, F or Cl; Z is H, F or CH3 ; R(1) is aryl or hetaryl; n and m are zero or 1; R(2) is alkyl or --(CH2)2 --OCH3 ; R(3) is H or methyl. They are obtained by reacting a compound of the formula II, STR2 in which R(5) is OH, with an activated carboxylic acid of the formula III, The compounds I have a very strong local and topical antiinflammatory action and exhibit a very good ratio of local to systemic antiinflammatory effects, which ratio is often markedly superior to that of analogous corticoid 17-alkyl carbonate 21-esters which do not carry any aryl or heteraryl group in the 21-ester radical.
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- Herbicidal Thienylureas, I
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Syntheses of the title substances as potential herbicides are described by a modified Curtius degradation of corresponding thiophene carboxylic acids, obtained in turn by haloform reaction of appropriate acetyl thiophenes.Regioselective substitution reactions of thiophenes were key steps for the construction of desired substitution patterns.Structure-activity considerations show that especially the 3-thienyl ureas 36 and 38 exhibit significant herbicidal activity comparable with commercial products. - Keywords: Curtius degradation; Herbicides; Thiophenes; Ureas; Urethanes
- Stanetty, Peter,Puschautz, Erhard,Friedbacher, Gernot
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- BECKMANN REARRANGEMENT OF ACETYLTHIOPHENE OXIME BENZENESULFONATES AS A METHOD FOR THE SYNTHESIS OF ACETAMIDOTHIOPHENES
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The Beckmann rearrangement of 2-acetylthiophene, 5-methyl-2-acetylthiophene, 5-chloro-2-acetylthiophene, and 2,5-dichloro-3-acetylthiphene oxime benzenesulfonates to the corresponding acetamidothiophenes was carried out by heating with an aqueous methanol solution of sodium acetate.This method can be used for the preparative synthesis of 2-acetamidothiophene and 2,5-dichloro-3-acetamidothiophene.
- Fabrichnyi, B. P.,Bulgakova, V. N.,Gol'dfarb, Ya. L.
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p. 401 - 403
(2007/10/02)
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- CARBOXYLATION OF 1,3-DIMETHYLURACIL AND THIOPHENES WITH CARBON MONOXIDE AND PALLADIUM(II) ACETATE IN THE PRESENCE OF SODIUM PEROXODISULFATE
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Treatments of 1,3-dimethyluracil and of thiophenes with palladium(II) acetate and sodium peroxodisulfate under a carbon monoxide atmosphere gave 1,3-dimethyluracil-5-carboxylic acid and the corresponding thiophene-2-carboxylic acids, respectively.
- Itahara, Toshio
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p. 127 - 128
(2007/10/02)
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