64992-14-9Relevant academic research and scientific papers
Preparation method of theophylline sodium salt
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Paragraph 0041-0042; 0050-0052; 0058-0059; 0065-0066, (2020/09/08)
The invention relates to the technical field of pharmaceutical chemicals, and particularly discloses a preparation method of theophylline sodium salt. The preparation method of theophylline sodium salt comprises the following process steps: mixing cyanoacetic acid and acetic anhydride for reaction to obtain mixed anhydride, and performing a condensation reaction on the mixed anhydride and 1,3-dimethylurea to obtain 1,3-dimethyl cyanoacetylurea; sequentially carrying out cyclization, nitrosation, hydrogenation and acylation on the 1,3-dimethyl cyanoacetylurea to obtain 1,3-dimethyl-4-amino-5-formylamino uracil; subjecting the 1,3-dimethyl-4-amino-5-formylamino uracil to ring closing to obtain the theophylline sodium salt. According to the preparation method, the reaction conditions are mildand easy to control, the product yield is high, byproducts are few, strong ammonia gas smell is avoided, the cost is low, and generated pollution wastes are few.
Preparation method of tofacitinib citrate
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Paragraph 0046; 0054; 0060; 0068; 0074; 0082, (2020/02/14)
The invention relates to the field of medicine synthesis, and particularly discloses a preparation method of tofacitinib citrate. The preparation method comprises the following steps: S1, dissolving acompound SM1, a compound SM2 and an alkaline reagent in a solvent A, and performing a reaction to obtain a first compound; S2, taking and mixing a catalyst, a solvent B and the first compound, introducing hydrogen, and carrying out a catalytic hydrogenation reaction to obtain a second compound; S3, taking and mixing active anhydride, a solvent C and the second compound, and carrying out an acylation reaction to obtain a third compound, wherein R in the active anhydride comprises an alkyl group or an aryl group; and S4, taking and mixing citric acid, a solvent D and the third compound, and carrying out a salt-forming reaction to obtain a compound T that is the tofacitinib citrate. The preparation method has the advantages of easily available initial raw materials, no use of complex or toxic compounds, short synthesis process route, simple and convenient reaction operation of each step, high total yield and high productivity, and is suitable for large-scale industrial production.
Identification and Optimization of Novel Small c-Abl Kinase Activators Using Fragment and HTS Methodologies
Simpson, Graham L.,Bertrand, Sophie M.,Borthwick, Jennifer A.,Campobasso, Nino,Chabanet, Julien,Chen, Susan,Coggins, Julia,Cottom, Josh,Christensen, Siegfried B.,Dawson, Helen C.,Evans, Helen L.,Hobbs, Andrew N.,Hong, Xuan,Mangatt, Biju,Munoz-Muriedas, Jordi,Oliff, Allen,Qin, Donghui,Scott-Stevens, Paul,Ward, Paris,Washio, Yoshiaki,Yang, Jingsong,Young, Robert J.
supporting information, p. 2154 - 2171 (2019/02/26)
Abelson kinase (c-Abl) is a ubiquitously expressed, nonreceptor tyrosine kinase which plays a key role in cell differentiation and survival. It was hypothesized that transient activation of c-Abl kinase via displacement of the N-terminal autoinhibitory "myristoyl latch", may lead to an increased hematopoietic stem cell differentiation. This would increase the numbers of circulating neutrophils and so be an effective treatment for chemotherapy-induced neutropenia. This paper describes the discovery and optimization of a thiazole series of novel small molecule c-Abl activators, initially identified by a high throughput screening. Subsequently, a scaffold-hop, which exploited the improved physicochemical properties of a dihydropyrazole analogue, identified through fragment screening, delivered potent, soluble, cell-active c-Abl activators, which demonstrated the intracellular activation of c-Abl in vivo.
l-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moiety via sustainable sonochemical approach
Ibrahim, Hamada Mohamed,Ahmed Arafa, Wael Abdelgayed,Behbehani, Haider
, p. 37606 - 37617 (2018/11/26)
The efficient, highly convenient synthesis of polysubstituted pyridine derivatives was established via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidene malononitriles and arylidene ethyl cyanoacetates in the presence of l-proline as an efficient organocatalyst for this type of ultrasonic-mediated Michael addition. The mechanistic pathway and factors affecting this reaction were also established. The main characteristics of this procedure are high yields, use of a cost-effective catalyst, and easy work-up and purification.
Studies on 3-oxoalkanenitriles: Novel rearrangement reactions observed in studies of the chemistry of 3-heteroaroyl-3-oxoalkanenitriles as novel routes to 2-dialkylaminopyridines
Al-Matar, Hamad M.,Khalil, Khaled D.,Al-Kanderi, Mona F.,Elnagdi, Mohamed H.
experimental part, p. 897 - 909 (2012/03/10)
3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of c
Applications of 2-arylhydrazononitriles in synthesis: Preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities
Behbehani, Haider,Ibrahim, Hamada Mohamed,Makhseed, Saad,Mahmoud, Huda
experimental part, p. 1813 - 1820 (2011/05/06)
In this effort, 2-arylhdrazononitriles were used as key synthons for the preparation of wide variety of new, uniquely substituted heterocyclic substances. In addition, the results of biological evaluations demonstrate that members of the group prepared ha
Synthesis of 7-substituted pyrazolo[1,5-a]pyrimidine-3-carboxamides as potential non benzodiazepine hypnotics
Behbehani, Haider,Ibrahim, Hamada Mohamed,Makhseed, Saad
experimental part, p. 267 - 282 (2010/08/07)
A variety of new pyrazolo[1,5-a]pyrimidines has been prepared as potential drugs for the treatment of insomnia. The general synthetic route used for this purpose involves the condensation of substituted cyanoacetamides 5a-c, prepared by reaction of cyanoacetic acid with amines in presence of acetic anhydride, with dimethylformamide dimethylacetal and subsequent treatment of the formed enamines 6 with hydrazine hydrate. This process affords the corresponding aminopyrazole carboxamides 9 that react with the enaminonitrile 12 to generate the targets. Structures of the substance prepared in these sequences were established by using spectroscopic methods, including 15N HMBC and NOE difference experiments, as well as X-raycrystallographic analysis.
Studies with enaminones and enaminonitriles: synthesis of 3-aroyl and 3-heteroaroyl-pyrazolo-[1,5-a]pyrimidines
Khalil, Khaled D.,Al-Matar, Hamad M.,Al-Dorri, Doa'a M.,Elnagdi, Mohamed H.
experimental part, p. 9421 - 9427 (2009/12/28)
The reaction of electron rich aromatics with cyanoacetic acid and acetic anhydride afforded 3-oxoalkanenitriles. Indium trichloride was used as a Lewis acid catalyst when the aromatic ring was not?sufficiently reactive. The synthesized 3-oxoalkanenitriles were subsequently condensed with dimethylformamide dimethylacetal (DMFDMA) to yield enaminones that reacted readily with hydrazine hydrate to yield 4-aroylpyrazole-3-amines. The 4-aroylpyrazole-3-amines were condensed with enaminones to yield 3-aroylpyrazolo[1,5-a]pyrimidines.
The reaction of cyclohexanone azine with cyanoacetic acid-acetic anhydride
Nakhai, Azadeh,Raftery, Jim,Bergman, Jan,Joule, John A.
experimental part, p. 1513 - 1516 (2009/04/07)
(Chemical Equation Presented) The reaction of cyclohexanone azine with a reagent produced by brief heating of cyanoacetic acid with acetic anhydride produced a highly substituted dihydropyrazolone.
