52449-98-6Relevant articles and documents
Palladium-Catalyzed Migratory Insertion of Carbenes and C-C Cleavage of Cycloalkanecarboxamides
Zhang, Peng,Zeng, Jia,Pan, Ping,Zhang, Xue-Jing,Yan, Ming
supporting information, p. 536 - 541 (2022/01/20)
A palladium catalyzed reaction of cycloalkanecarboxamides and diazomalonates or bis(phenylsulfonyl)diazomethane has been developed. The reaction proceeds via carbene migratory insertion and cascade C-C cleavage pathways. Cycloalkanecarboxamides with four to seven membered rings are applicable in the transformation. A series of ring opening products were prepared with moderate yields. The finding provides valuable clues for the development of new reactions involving carbene migratory insertion and the cleavage of unstrained C(sp3)-C(sp3) bonds.
Lappaconitine derivative with analgesic activity, and preparation method and application thereof
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Paragraph 0363-0368, (2021/07/14)
The invention provides a lappaconitine derivative with analgesic activity, and a preparation method and application thereof. The structure of the lappaconitine derivative is as shown in formula I in the specification. The lappaconitine derivative provided by the invention is high in analgesic activity, good in water solubility and low in biotoxicity, can be used for preparing low-toxicity analgesic drugs, and is wide in application prospect.
The parmodulin NRD-21 is an allosteric inhibitor of PAR1 Gq signaling with improved anti-inflammatory activity and stability
Gandhi, Disha M.,Rosas, Ricardo,Greve, Eric,Kentala, Kaitlin,D.-R. Diby, N'Guessan,Snyder, Vladyslava A.,Stephans, Allison,Yeung, Teresa H.W.,Subramaniam, Saravanan,DiMilo, Elliot,Kurtenbach, Khia E.,Arnold, Leggy A.,Weiler, Hartmut,Dockendorff
supporting information, p. 3788 - 3796 (2019/07/17)
Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activi
Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery
Kirichok, Alexander A.,Shton, Irina O.,Pishel, Irina M.,Zozulya, Sergey A.,Borysko, Petro O.,Kubyshkin, Vladimir,Zaporozhets, Olha A.,Tolmachev, Andrei A.,Mykhailiuk, Pavel K.
supporting information, p. 5444 - 5449 (2018/04/23)
The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps—synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
Improved method used for preparing quinazoline drugs
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Paragraph 0032; 0038, (2018/07/06)
The invention relates to an improved method used for preparing quinazoline drugs, and provides a synthesis route taking 2-chloro-4-amino-6,7-dimethoxyquinazoline as an intermediate. The synthesis route comprises following steps: acrylonitrile and a methylamine alcohol solution are subjected to amination reaction so as to obtain intermediate (I); triethylamine is taken as an acid binding agent, andbenzyl chloride is taken as a protective group so as to obtain an intermediate (II); a metal hydride is adopted so as to obtain an intermediate (III) through reduction; acylation with tetrahydro-2-furancarbonylchloride is carried out so as to obtain an intermediate (IV); the intermediate (IV) and ammonium formate are subjected to hydrogenolysis under catalytic effect of palladium on carbon so asto obtain an intermediate (V); and at least condensation reaction with 2-chloro-4-amino-6,7-dimethoxyquinazoline is carried out so as to obtain quinazoline drug Alfuzosin Hydrochloride (VI). Comparedwith the prior art, the improved method possesses following advantages: operation is simple and safe; reaction conditions are convenient to control; energy consumption is low; yield is stable; and industrialized application prospect is promising.
A process for the preparation of alfuzosin hydrochloride method (by machine translation)
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Paragraph 0023; 0024; 0027, (2017/08/29)
The invention relates to a process for the preparation of alfuzosin hydrochloride method, method comprises the following steps: (1) 15 °C following, acrylonitrile into the the methylamine is mellow solution to stir, by distillation to obtain (I); (2) to (I) is dripped reducing agent in an organic solvent, heating to reflux, then slowly sequentially into the 25% sodium hydroxide solution and distilled water, by the distillation treatment to obtain the (II); (3) under dry condition, the thionyl chloride is slowly dripped into the 2 - tetrahydrofuran formic acid, a 2 - tetrahydrofuran chloride; (4) the temperature control in the 5 - 15 °C conditions, will be 2 - tetrahydrofuran formyl the chlorine drips into containing acid, organic solvent and (II) of the mixed solution, then completing the stirring 3 hours, for 25% sodium hydroxide solution to neutralize, by organic solvent extraction, (III) be; (5) to (III) with 2 - chloro - 4 - amino - 6, 7 - dimethoxy quinazoline in presence of organic solvent, reflux stirring 4 - 10 hours, cooling and filtering, and steaming and removing the organic solvent, acetone dispersed precipitate solid, then re-crystallizing mixed solvent, to get the alfuzosin hydrochloride (IV). (by machine translation)
2-thioquinazolinedione derivatives
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Paragraph 0076; 0077; 0078, (2017/07/20)
The invention belongs to the field of medicine and chemical industry, and in particular, relates to 2-thioquinazolinedione derivatives and a use thereof in drugs. Specifically, the invention relates to compounds having the use of inhibiting poly(ADP-ribose) polymerase activity, wherein the enzyme is also known as poly(ADP-ribose) synthetase and polyADP-ribosyltransferase, and is commonly known as PARP. The compounds have the following characteristics described in the specification. In the compounds represented by the formula (I), A and D together represent substituted fused aromatic rings; X can be NRX or CRXRY; if X is NRX, n is 1 or 2; if X is CRXRY, n is 1; RX can be selected from H, substitutive C1-20 alkyl, C5-20 aryl, C3-20 heterocyclic group, amide, thioamide, ester, acyl and sulfonyl; RY is selected from H, hydroxyl, amino and the like; or RX and RY can together form a spiro-C3-7 cyclic hydrocarbon group or a heterocyclic group; R2 and R3 are both H, or when X=CRXRY, R2, R3, RX, and RY and carbon atoms connected therewith can form a substitutive fused aromatic ring; and R1 is selected from H or halogen.
Industrial preparation method of acetyl tetrahydrofuran with high optical purity
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Paragraph 0011; 0029, (2016/10/08)
The invention discloses an industrial preparation method of acetyl tetrahydrofuran with a high optical purity, and belongs to the field of chemical synthesis. According to the preparation method, tetrahydrofuroic acid is taken as the raw material and then is chlorinated to obtain tetrahydrofuran carbonyl chloride, tetrahydrofuran carbonyl chloride and Meldrum's acid carry out condensation reactions, and reaction product is hydrolyzed to obtain the target compound namely acetyl tetrahydrofuran. The preparation method has the advantages that the raw material cost is low, the preparation method does not need any Grignard reagent, the product property is stable, the purity can reach 98% or more, the optical purity can reach 99% or more, and the yield can reach 70% or more. The method has applied to industrial production. The product quality is stable. The reaction conditions are mild. The operation is safe and reliable. Dichloromethane can be recycled. The technology has the advantages of good repeatability and low preparation cost, and is a reliable industrial production method of acetyl tetrahydrofuran with a high optical purity.
Safe, selective, and high-yielding synthesis of acryloyl chloride in a continuous-flow system
Movsisyan, Marine,Heugebaert, Thomas S. A.,Dams, Rudy,Stevens, Christian V.
, p. 1945 - 1952 (2018/08/17)
Acid chlorides are an important class of compounds and their high reactivity and instability has prompted us to develop a straightforward procedure for their synthesis with ondemand and on-site synthesis possibilities. The focus of this report is acryloyl chloride, mainly important for the acrylate and polymer industry. A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride. Three routes were investigated in a microreactor setup and all three can potentially be used for its production. The methodology was further expanded to the synthesis of other unstable acid chlorides by both the thionyl chloride and the oxalyl chloride mediated processes. The most sustainable method was the oxalyl chloride mediated procedure under solvent-free conditions, in which nearequimolar amounts of carboxylic acid and oxalyl chloride were used in the presence of catalytic amounts of DMF at room temperature. Within 1 to 3 min, nearly full conversions into the acid chlorides were achieved.
Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp3 C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems
Parella, Ramarao,Babu, Srinivasarao Arulananda
, p. 2339 - 2355 (2015/06/01)
An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp3 C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp3)-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7.
