4318-56-3Relevant articles and documents
Synthesis method of 6-chloro-3-alkyl uracil
-
Paragraph 0030; 0032; 0047; 0049; 0050; 0052, (2019/12/02)
The invention relates to a synthesis method of 6-chloro-3-alkyl uracil, which is characterized by comprising the following steps: by using malonic acid and N-alkyl urea as raw materials, carrying outthe cyclization reaction to generate alkyl tripyrimidone; and then carrying out chlorination on the alkyl tripyrimidone to generate the 6-chloro-3-alkyl uracil. Compared with an existing method, the method is mild in reaction and low in cost, high-cost and high-risk raw materials such as high-toxicity and high-boiling phosphorus oxychloride are not used, and industrial large-scale production is facilitated; meanwhile, the chemical purity obtained by the method is high, the yield is good, and the economic benefit is good.
A curved geleg sandbank preparation method
-
Paragraph 0050; 0052; 0054; 0066; 0068; 0070; 0082; 0084, (2019/04/04)
The invention claims a curved geleg sandbank preparation method, using methyl urea and malonic acid diethyl ester as an initial raw material for preparing 3 - methyl - 6 - chloro uracil, while at the same time by the 2 - hydroxymethyl - 4 - pentachloro as initial material to prepare 2 - chloromethyl - 4 - pentachloro, then the 3 - methyl - 6 - chloro uracil with 2 - chloromethyl - 4 - pentachloro prepared tune geleg sandbank, the material cost is low, the preparation process is easy to control, convenient for industrial production.
Preparation method of 6-chloro-3-methyluracil
-
Paragraph 0021; 0027; 0030-0033; 0036-0039; 0042-0045; 0048, (2019/01/08)
The invention belongs to the technical field of medicine chemosynthesis, and relates to a preparation method of 6-chloro-3-methyluracil. The method comprises the following steps that 1, methylurea, anorganic solvent and alkali are added into a reaction container for stirring and dissolution, then malonic acid or malonic ester is added, heating and reflux are conducted, then cooling is conducted,acid is added to adjust a pH value of reaction liquid, water is added, the reaction liquid is cooled, suction filtration is conducted, and drying is conducted to obtain a white to off-white first intermittent in a shape of loose powder; 2, phosphorus oxychloride is used for chloridizing the first intermittent to obtain a crude product; 3, the crude product prepared in the step 2 is subjected to decoloration by means of activated carbon to obtain a finished product. According to the preparation method of the 6-chloro-3-methyluracil, the product in the step 1 precipitates in a form of sodium salt, that is to say, the first intermittent is 1-sodium methylbarbiturate, compared with the prior art where a first intermittent precipitates in a form of 1-methylbarbituric acid, the preparation method of the 6-chloro-3-methyluracil has the advantages that the yield is obviously improved, moreover, in the step 2, acetonitrile is used as the solvent, the phosphorus oxychloride usage is reduced, post-treatment is convenient, and meanwhile, the product has a good crystal form, and is easy to filter.
Preparation method for trelagliptin
-
Paragraph 0031; 0032, (2018/03/26)
The invention discloses a preparation method for trelagliptin and belongs to the field of organic synthesis. The preparation method comprises the following steps: (1) taking methylurea and diethyl malonate as initial raw materials and performing cyclization and chlorination reaction, thereby acquiring 3-methyl-6-chlorouracil; (2) acquiring 2-(6-chlorine-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-methyl)-4-fluorobenzonitrile from the nucleophilic substitution reaction of 3-methyl-6-chlorouracil and 2-bromine methyl-4-fluorobenzonitrile; (3) generating a target compound (R)-2-((6-(3-aminopiperidines-1-group)-3-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-group) methyl-4-fluorobenzonitrile (trelagliptin) through the reaction of 2-(6-chlorine-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-methyl)-4-fluorobenzonitrile and (R)-3-aminopiperidine. The preparation method has the characteristics of low-cost and easily acquired initial raw materials, convenient after-treatment, mild condition, operation convenience, and the like.
Convenient synthesis of toxoflavin that targets β-catenin/TCF4 signaling activities
Mao, Yongjun,Tian, Wang,Huang, Ziwei,An, Jing
, p. 594 - 597 (2014/06/10)
A rapid and improved route for synthesis of toxoflavin, an antibiotic and antitumor agent, is described. The method uses easily obtained materials and simple and practical reactions, including chlorination, condensation, and diazotization to produce toxoflavin in five steps with 14.2% yield and 98.6% purity (HPLC). This synthetic toxoflavin effectively inhibited β-catenin/Tcf4 driven TOP-luciferase activity with an IC50 of less than 0.5 μM and induced colon cancer cell death in a dose-dependent manner with an IC50 of 0.29 μM.
Planar chiral flavinium salts: Synthesis and evaluation of the effect of substituents on the catalytic efficiency in enantioselective sulfoxidation reactions
Jurok, Radek,Hodacova, Jana,Eigner, Vaclav,Dvorakova, Hana,Setnicka, Vladimir,Cibulka, Radek
supporting information, p. 7724 - 7738 (2013/12/04)
A series of substituted planar chiral flavinium salts with a phenyl "cap" have been prepared as potential catalysts for enantioselective sulfoxidation reactions with hydrogen peroxide by using an approach based on the synthesis of (arylamino)uracils and their condensation with substituted nitrosobenzenes. The effect of substituents at various positions on the ability of the catalyst to promote enantioselective sulfoxidation recations was investigated. Introduction of the tyrosine group into the side-chain of the flavinium species or substitution of the nitrogen N-3 of the flavin unit by o-isopropylphenyl has a remarkably positive effect on the enantioselectivity of the sulfoxidation reactions of aromatic and aliphatic substrates, respectively. On the other hand, substitution of the phenyl "cap" led to a substantial decrease in the efficiency of the catalyst. In summary, optimisation of the structures of the planar chiral flavinium catalysts led to enantioselectivities of up to 61 % ee for aromatic sulfides and of up to 65 % ee for tert-butyl methyl sulfide. By making structural changes to the planar chiral flavinium catalysts, the enantioselectivities of the sulfoxidation of aryl methyl sulfides and tert-butyl methyl sulfide with hydrogen peroxide have been improved. Copyright
Microwave-assisted synthesis of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5, 7(1H,6H)-dione libraries: Derivatives of toxoflavin
Todorovic, Nick,Giacomelli, Andrew,Hassell, John A.,Frampton, Christopher S.,Capretta, Alfredo
experimental part, p. 6037 - 6040 (2010/11/21)
The parallel synthesis of a library of toxoflavin derivatives is described. The microwave-assisted approach involves the de novo generation of the heterocyclic scaffold and allows for facile introduction of a variety of fragments.
Planar chiral flavinium salts - Prospective catalysts for enantioselective sulfoxidation reactions
Jurok, Radek,Cibulka, Radek,Dvorakova, Hana,Hampl, Frantisek,Hodacova, Jana
supporting information; experimental part, p. 5217 - 5224 (2010/11/02)
A novel planar chiral flavinium salt, 3-benzyl-5-ethyl-10-(8- phenylnaphthalen-1-yl)isoalloxazinium perchlorate (2b), which bears a phenyl cap that covers one side of the isoalloxazinium skeleton plane, has been prepared as a potential catalyst for the enantioselective H2O2 oxidation of sulfides. The rate of H2O2 oxidation of sulfides in the presence of racemic 2b is comparable to that of the reaction catalysed by 5-ethyl-3,10-dimethylisoalloxazinium perchlorate, which indicates that the bulky shielding substituent does not influence the catalytic activity of the flavinium unit. The turnover frequency for the oxidation of thioanisole with hydrogen peroxide with 2b is 870 h-1. The enantiomerically pure salts (+)-2b and (-)-2b were prepared from the pure enantiomers (+)-3b and (-)-3b of 3-benzyl-10-(8-phenylnaphthalen-1-yl)isoalloxazine (3b) obtained by HPLC separation of racemic 3b on a chiral stationary phase. The enantiomerically pure salts (+)-2b and (-)-2b catalyse the H2O2 oxidation of para-substituted thioanisoles with enantiomeric excesses of 34-44%. The highest enantioselectivity (54% ee) was observed in the oxidation of methyl naphthyl sulfide.
ORGANIC COMPOUNDS
-
Page/Page column 76, (2009/07/17)
1- or 2- or 7-(substituted)-3-(optionally hetero)arylamino-[lH, 2H]-pyrazolo[3,4-d] pyrimidine-4,6(5H, 7H)-dione derivatives, in free, salt or prodrug form, are useful as pharmaceuticals, particularly as phosphodiesterase 1 inhibitors, useful for the treatment of diseases involving disorders of the dopamine Dl receptor intracellular pathway, such as Parkinson's disease, depression, narcolepsy and damage to cognitive function, e.g., in schizophrenia or disorders that may be ameliorated through enhanced progesterone - signaling pathway, e.g., female sexual dysfunction.
Synthesis, biological active molecular design, and molecular docking study of novel deazaflavin-cholestane hybrid compounds
Shrestha, Ajaya R.,Shindo, Takashi,Ashida, Noriyuki,Nagamatsu, Tomohisa
body text, p. 8685 - 8696 (2009/04/11)
Novel deazaflavin-cholestane hybrid compounds, 3′,8′-disubstituted-5′-deazacholest-2,4-dieno[2,3-g]pteridine-2′,4′(3′H,8′H)-diones, have been synthesized by condensation reaction between 6-(monosubstituted amino)-pyrimidin-2,4(1H,3H)-diones and 2-hydroxymethylenecholest-4-en-3-one in presence of p-toluenesulfonic acid monohydrate and diphenyl ether. The antitumor activities against human tumor cell lines (CCRF-HSB-2 and KB cells) have been investigated in vitro, and many of these compounds showed promising antitumor activities. Furthermore, molecular docking study using LigandFit within the software package Discovery Studio 1.7 was done for lead optimization of these compounds as potential PTK inhibitors. In general, all of the synthesized steroid-hybrid compounds showed good binding affinities into PTK (PDB code: 1t46).
