27514-08-5Relevant articles and documents
Synthesis and separation method of pramipexole intermediate
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Paragraph 0018, (2020/05/01)
The invention discloses a synthesis and separation method of a pramipexole intermediate. The synthesis and separation method comprises the following steps: (1) synthesis of 4-acetamino cyclohexanone;(2) synthesis of 2-amino-6-acetamino-4,5,6,7-tetrahydrobenzothiazole; (3) synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole; (4) synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole; and (5) purification of D-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole: recrystallizing levotartaric acid ammonium salt obtained in the step (4) by using purified water, then dissolving recrystallized solidsin purified water, adjusting the pH value, carrying out stirring crystallization, filtering, sequentially pulping, stirring, washing and leaching a filter cake by using ice water of 0-5 DEG C, and drying to obtain 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole. According to the synthesis and separation method of the pramipexole intermediate, after the intermediate 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole is obtained through a reasonable synthesis reaction, a dextral compound is separated and purified through proper steps, and the synthesis and separation method has important milestone significance for preparing high-purity and high-quality pramipexole.
Overcoming Problems at Elaboration and Scale-up of Liquid-Phase Pd/C Mediated Catalytic Hydrogenations in Pharmaceutical Production
Tungler, Antal,Szabados, Erika
, p. 1246 - 1251 (2016/07/23)
The practical solutions for scale-up and production of intermediates or precursors of pharmaceuticals by liquid-phase Pd/C mediated hydrogenation can be of considerable interest and deserve broader attention even if they have not been the focus of previously published research due to regulations of patent law. The practical obstacles are persistent and have been known for a long time, but for the most part remained unpublished. The most important discoveries and solutions that contributed to the successful scale-up of hydrogenations for pharmaceutical production were the following: (i) the poisoning of Pd/C catalyst with Fe2+ ions for the selective hydrogenation of 2,6-dimethyl-1-nitrosopiperidine to the corresponding hydrazo compound; (ii) alloying of the deposited Pd metal with Cu for converting the aromatic acid chlorides into the corresponding aldehydes; (iii) alteration of the pH of the reaction mixture to basic values which enhanced the stereoselectivity of paracetamol hydrogenation; (iv) a useful modification of the catalyst preparation process, i.e., the acidification of the catalyst resulted in the hydrogenolysis of benzylic OH in a molecule containing a basic N atom; (v) use of two liquid phases, altogether a four-phase system, which permitted the hydrogenolysis of the S-S bond in a potential catalyst poisoning molecule; (vi) the preservation of the metallic Pd surface of the catalyst by saturation of the reaction mixture with hydrogen, resulting in a high H2/substrate ratio, increased the aldehyde yield in the hydrogenation of 4-chloro-butyric-acid-chloride by avoiding the unwanted poisoning effect of the hydrochloric acid. In the present article, these problems and their solutions, as they emerged during the scale-up of the processes, will be discussed in detail.
Selective hydrogenation of paracetamol to acetamidocyclohexanone with silylated SiO2 supported Pd-based catalysts
Song, Wenjing,Liu, Xiuna,Jiang, Shaoyang,Chen, Zhou,Weng, Weizheng,Rodríguez-Ramos,Yi, Xiaodong,Fang, Weiping
, p. 41572 - 41579 (2016/05/19)
A series of catalysts comprising well-distributed Pd nanoparticles incorporated on silylated SiO2 were fabricated by the wet impregnation method and investigated in the selective hydrogenation of paracetamol to 4-acetamidocyclohexanone. The catalysts calcined at different temperatures were characterized by TG, FT-IR, N2 physisorption, TPR and XPS. The results showed that organic modification led to a catalyst surface composed of stable Si-(CH3)3 species even after calcination at 300 °C. Also, changes occurred in the size and electronic properties of the Pd particles through the different amounts of grafted groups on the SiO2 support. The mode of adsorption of the paracetamol molecule was influenced by the quite bulky organic groups on the support, resulting in a significant improvement in selectivity towards 4-acetamidocyclohexanone and preventing full hydrogenation to some extent. The best result was obtained on the silylated Pd catalyst calcined at 500 °C, with 64.9% selectivity to keto at the paracetamol conversion of 60.5%, while the non-silylated SiO2 supported Pd catalyst gave 4-acetamidocyclohexanone selectivity of 29.1% at 53.8% conversion.
AMINOPIPERIDINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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Page/Page column 25, (2010/11/28)
The present invention relates to compounds of formula (I) as defined herein that are melanocortin receptor agonists, to the preparation thereof and to the therapeutic use thereof in the treatment and in the prevention of obesity, diabetes and sexual dysfunctions that can affect both sexes, in the treatment of cardiovascular diseases, and also in anti-inflammatory uses or in the treatment of alcohol dependency.
Ruthenium-supported catalysts for the stereoselective hydrogenation of paracetamol to 4-trans-acetamidocyclohexanol: Effect of support, metal precursor, and solvent
Bachiller-Baeza,Guerrero-Ruiz,Rodriguez-Ramos
, p. 439 - 445 (2007/10/03)
The influence of the support, the metal precursor, and the solvent on the selective hydrogenation of paracetamol (4-acetamidophenol) was studied over supported ruthenium catalysts. The catalysts supported on the oxidic supports Al2O3 and SiO2 gave the best results in terms of activity, selectivity for the acetamidocyclohexanols (99%), and stereoselectivity for the trans isomer (53 and 46%, respectively). Carbon-supported catalysts produced larger amounts of secondary compounds, mainly N-cyclohexylacetamide, which was derived from the hydrogenolysis reaction of the OH group. The use of a chloride precursor resulted in the enhancement of the formation of N-cyclohexylacetamide and partially hydrogenated products; the stereoselectivity also increased. Moreover, because of the acidity caused by residual Cl, condensation led to oligomers of paracetamol. In spite of the decrease in the selectivity for cyclohexanol derivatives when the more polar solvent ethanol was used instead of isopropanol or tetrahydrofuran the stereoselectivity for the trans isomer increased from 30 to 38%. The results confirm that the factors studied affect the mode of adsorption of the molecule of paracetamol on the catalyst in different ways. These effects determine the product distribution and the selectivity of the reaction.
PROCESS FOR PREPARING 2,6-DIAMINO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE
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Page 2; 6, (2008/06/13)
2,6-diamino-4,5,6,7-tetrahydro-benzothiazole, which is useful for making pramipexole, is made by: (i) reacting bromine with a solution of 4-acetamido-cyclohexanone in water to produce 2-bromo-4-acetamido-cyclohexanone; (ii) after step (i), adding thiourea to produce 6-acetyl amino- 2-amino-4,5,6,7-tetrahydro-benzthiazole; (iii) after step (ii), adding an aqueous solution of hydrobromic acid to produce 2,6-diamino-4,5,6,7-tetrahydro-benzthiazole dihydrobromide; and (iv) after step (iii), isolating 2,6-diamino-4,5,6,7 -tetrahydro-benzthiazole.
Synthesis of 2-amino-7,8-dihydro-6(5H)-quinazolinone, 2,4-diamino-7,8- dihydro-6(5H)-quinazolinone, 5,6,7,8-tetrahydro-2,6-quinazolinediamine and 5,6,7,8-tetrahydro-2,4,6-quinazolinetriamine derivatives
Marinko, Petra,Obreza, Ales,Peterlin-Masic, Lucija,Krbavcic, Ales,Kikelj, Danijel
, p. 405 - 409 (2007/10/03)
N-(2-Amino-5,6,7,8-tetrahydro-6-quinazolinyl)acetamide (9) and N-(2,4- diamino-5,6,7,8-tetrahydro-6-quinazolinyl)acetamide (6) were synthesized from N-(4-oxocyclohexyl)acetamide (5) as novel peptidomimetic building blocks. With similar purpose, N-(6-oxo-5,6,7,8-tetrahydro-2-quinazolinyl)acetamide (18) and N-[2-(acetylamino)-6-oxo-5,6,7,8-tetrahydro-4-quinazolinyl]acetamide (14) were prepared from cyclohexane-1,4-dione monoethylene ketal (11).
Tricyclic compounds and drug compositions containing the same
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, (2008/06/13)
Compounds having a β-3 adrenaline receptor agonist and are useful as drugs for the treatment and prevention of diabetes, obesity, hyperlipemia, etc., represented by a general formula (I) and salts thereof, and a process for producing these, and their intermediates, wherein R represents hydrogen or methyl; R1 represents hydrogen, halogen, hydroxy, benzyloxy, amino, or hydroxymethyl; R2 represents hydrogen, hydroxymethyl, NHR3, SO2 NR4 R4', or nitro; R6 represents hydrogen or lower alkyl; and X represents nitrogen, R9 represents hydrogen, one of R7 and R8 represent hydrogen, and the other thereof represents hydrogen, amino, acetylamino, or hydroxy.
Process for preparing substituted cyclohexanones
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, (2008/06/13)
Substituted cyclohexanones of the formula STR1 where R1 to R5 are as defined in the description, can be obtained by catalytic hydrogenation of phenols of the formula STR2 where R1 to R5 are as defined in the description. The reaction is carried out at from 20° to 250° C., from 1 to 200 bar and in an ether as solvent. If desired, an alkaline alkali metal, alkaline earth metal or ammonium compound is used as additive.
Method for preparing aromatic secondary amino compound
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, (2008/06/13)
Disclosed are (1) a method for preparing an aromatic secondary amino compound which comprises reacting an N-cyclohexylideneamino compound in the presence of a hydrogen moving catalyst and a hydrogen acceptor by the use of a sulfur-free polar solvent and/or a cocatalyst, and (2) a method for preparing an aromatic secondary amino compound which comprises reacting cyclohexanone or a nucleus-substituted cyclohexanone, an amine and a nitro compound corresponding to the amine in a sulfur-free polar solvent in the presence of a hydrogen moving catalyst, a cocatalyst being added or not added. In a further aspect, a method is provided for the preparation of aminodiphenylamine by reacting phenylenediamine and cyclohexanone in the presence of a hydrogen transfer catalyst in a sulfur-free polar solvent while using nitroaniline as a hydrogen acceptor.
