18592-13-7Relevant articles and documents
Synthesis of a novel fused tricyclic heterocycle, pyrimido[5,4-e][1,4] thiazepine, and its derivatives
Bazazan, Tahmineh,Bakavoli, Mehdi,Rahimizadeh, Mohammad,Eshghi, Hossein,Nikpour, Mohsen
, p. 401 - 404 (2013)
Sequential treatment of 5-bromo-2,4-dichloro-6-(chloromethyl)pyrimidine with 2-aminothiophenol and secondary amines afforded a series of 2-[(5-bromo-2-chloro-6-aminopyrimidin-4-yl)methylthio]aniline derivatives. Reaction of the latter compounds with secondary amines in ethanol gave a family of new 5,7-diamino-5,11-dihydropyrimido[5,4-e][1,4]benzothiazepines.
Fragment-based approach to the design of 5-chlorouracil-linked-pyrazolo[1, 5-a][1,3,5]triazines as thymidine phosphorylase inhibitors
Sun, Lingyi,Li, Jiarong,Bera, Hriday,Dolzhenko, Anton V.,Chiu, Gigi N.C.,Chui, Wai Keung
, p. 400 - 410 (2013)
5-Chlorouracil-linked-pyrazolo[1,5-a][1,3,5]triazines were designed as new thymidine phosphorylase inhibitors based on the fragment based drug design approach. Multiple-step convergent synthetic schemes were devised to generate the target compounds. The intermediate 5-chloro-6-chloromethyluracil was synthesized by a 4-step reaction. A series of the second bicyclic intermediates, namely pyrazolo[1,5-a][1,3,5]triazin-2-thioxo-4-one, was obtained from various substituted 3-aminopyrazoles. These two intermediates were coupled finally in the presence of sodium ethoxide and methanol to yield the desirable target compounds. The methylthio coupling spacer was found to be suitable in enabling the interaction of the two fragments at the active site and allosteric site of the enzyme. The best coupled compound (9q) inhibited the thymidine phosphorylase with an IC50 value as low as 0.36 ± 0.1 μM. In addition, 9q demonstrated a mixed-type of enzyme inhibition kinetics, thus suggesting that it might indeed potentially bind at two different sites on the enzyme. Georg Thieme Verlag KG Stuttgart New York ISSN 0935-8943.
Purification method for uracil compound
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Paragraph 0024-0031, (2019/01/23)
The invention provides a purification method for a uracil compound, and belongs to the field of medical intermediate purification. The method comprises the steps that a uracil compound crude product obtained through preliminary purification is thermally dissolved in a polar aprotic solvent, a preliminarily purified uracil compound solid is precipitated through cooling and recrystallization, then an appropriate solvent is selected to carry out pulping on the uracil compound, pigment and other impurities contained in the uracil compound are dissolved, washed and dried to obtain the uracil compound with higher purity. The purification method for the uracil compound has the advantages that the uracil compound is purified by adopting an optimized recrystallization technology, the problem that the purification efficiency of a uracil compound in the prior art is low, in particular, the technical problem that a kilogram-level or tonnage-level of uracil compound in the prior art cannot be efficiently purified is solved, the production efficiency is improved, and the production cost is reduced.
A 6 - chloromethyl uracil synthetic method (by machine translation)
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, (2017/08/29)
The invention discloses a 6 - chloromethyl uracil synthetic method, comprises the following steps: (1) esterification reaction: the orotic adding anhydrous in methanol, adds by drops two chlorine Asia sulphone, reaction 6 hours, to evaporate the solvent, the organic solvent is added, stirring at the room temperature, filtered, and dried to get the orotic acid methyl ester; (2) reduction reaction: the methyl orotic dissolved in methanol, added to the Lewis acid, adding sodium borohydride, stirring at room temperature for 12 - 16 hours, ice for acetic acid neutralization, to evaporate the solvent, the organic solvent is added, stirring at the room temperature, filtering, drying, be 6 - hydroxy methyl uracil; (3) chlorinated reaction: the 6 - hydroxy methyl uracil in the added to the organic solvent, by adding thionyl chloride and a catalytic amount of N, N - dimethyl formamide, reaction 2 hours, cooled to the room temperature, filtering, drying, be 6 - chloro methyl uracil. Synthesis method of the invention, avoids the use of toxic reagents, mild reaction conditions, cheap, high yield, and is favorable for industrial production. (by machine translation)
