- A new method to synthesize famciclovir
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A new and efficient method has been reported for the synthesis of 2-amino-9-[4-acetoxy-3-(acetoxymethyl)butyl-1-yl]purine(famciclovir)starting from guanine. The route involves chlorination of guanine, optimized Mitsunobu reaction, coupling with diethyl malonate, hydrogenation, reduction and esterification,and the overall yield is about 29%. This method does not require any form of chromatographic purification to give pure famciclovir, and it is an industrially viable manufacturing process for this drug. The Japan Institute of Heterocyclic Chemistry.
- Luo, Lei,Chen, Guorong,Li, Yuanchao
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- Synthesis method of 2-amino-6-chloroguanine
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The invention provides a synthesis method of 2-amino-6-chloroguanine, the synthesis method comprises the following steps: synthesizing 2-amino-6-chloroguanine; according to the method disclosed by the invention, a route of a 2, 4, 5-triamino-6-chloropyrimidine intermediate is not adopted, but 4-chloro-5, 6-dinitropyrimidine-2-amine is taken as an intermediate, and 2-amino-6-chloroguanine is obtained by cyclization on the basis of the intermediate. The synthesis method has few steps, each step is easy to carry out, and the product is high in yield and high in purity, so that the total yield of the 2-amino-6-chloroguanine is relatively high; the method is suitable for industrial production of the 2-amino-6-chloroguanine, and has a wide commercial prospect.
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Paragraph 0052-0057
(2021/08/11)
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- Preparation methods for 2-amino-6-chloroguanine and intermediates of 2-amino-6-chloroguanine
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The invention provides preparation methods for 2-amino-6-chloroguanine and intermediates of the 2-amino-6-chloroguanine. The preparation method of the intermediates comprises the following steps: dissolving 2,4-diamino-5-nitroso-6-hydroxypyrimidine in a solvent A and N,N-dimethylformamide, conducting heating for refluxing, dropwise adding a triphosgene solution, carrying out a heat-preserved reaction, and after the reaction is finished, carrying out post-treatment to obtain an intermediate compound II of 2-amino-6-chloroguanine; and then, conducting further treatment to obtain intermediates III to IV and 2-amino-6-chloroguanine. According to the preparation methods of the 2-amino-6-chloroguanine and the intermediates of the 2-amino-6-chloroguanine, a synthesis method of the 2-amino-6-chloroguanine is adopted, so a process of carrying out a chlorination reaction on guanine, which is more expensive and serves as an initial raw material, and phosphorus oxychloride in the prior art is avoided, and meanwhile, the generation of a large amount of high-phosphorus and high-ammonia-nitrogen wastewater which is difficult to treat in the traditional process is avoided.
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Paragraph 0055; 0067; 0070-0071; 0075; 0078-0079
(2021/08/25)
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- Synthetic method 2 -amino -6 - chloropurine
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The invention provides a synthetic method of 2 - amino -6 - chloropurine, and belongs to the field of organic synthesis. The synthesis method provided by the invention comprises the following steps: adding 2 -acetyl-6-hydroxypurine into the reaction container. The product and comprises hexachloroacetone, organic base A chloride, heating reflux reaction 2h - 48h, distillation to remove dimethyl sulfoxide, adding alkali liquor pH, reacting 1h - 12h, adjusting 7.0 - 7.5 to 2 - and separating and purifying to obtain the amino -6 - chloropurine of the target product. The nitrogen-containing phosphorus-containing reagent is greatly reduced, the emission of nitrogen-containing phosphorus-containing wastewater is reduced correspondingly, and large-scale process production is facilitated.
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Paragraph 0048-0075
(2021/08/25)
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- Preparation method of purine nucleotide intermediate
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The invention relates to the technical field of medical intermediates, particularly to a preparation method of a purine nucleotide intermediate. The synthesis route of the preparation method comprises steps as follows: 1) carrying out a chlorination reaction on a raw material compound V and a thionyl chloride/hydrogen peroxide reaction system to obtain a compound IV; 2) reacting the compound IV with methylamine to obtain a compound III; and 3) reacting the compound III with a compound II in the presence of a catalyst to obtain a compound I. According to the invention, the synthetic route of the purine nucleotide intermediate is improved, the methylation is firstly carried out, and then the deprotection is carried out, so that the reaction condition is mild, the operation is simple, the yield and the purity are higher, and the method is suitable for industrial large-scale production.
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Paragraph 0028-0032; 0037-0041; 0046-0050
(2021/06/21)
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- Method for synthesizing 2-amino-6-chloropurine
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The invention discloses a method for synthesizing 2-amino-6-chloropurine, and belongs to the field of organic chemical synthesis. The synthesis method of the 2-amino-6-chloropurine comprises the following steps: enabling 6-hydroxyl-2,4,5-triaminopyrimidine to react with trimethyl orthoformate to generate guanine, and enabling the guanine to react with hydrogen chloride and hydrogen peroxide to generate 2-amino-6-chloropurine. The method has the advantages of short reaction time, high yield, no generation of a large amount of three wastes, simple operation, and facilitation of industrial production.
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Paragraph 0021-0035
(2020/09/08)
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- 2-amino-6-chloropurine as well as synthesis method, intermediate and application thereof
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The invention belongs to the technical field of medicines and in particular relates to 2-amino-6-chloropurine as well as a synthesis method, an intermediate and application thereof. The synthesis method of the 2-amino-6-chloropurine comprises the following steps: performing a primary reaction, namely mixing ethyl cyanoacetate, chloroformamidine hydrochloride, liquid ammonia and sodium to implementa reaction so as to generate an intermediate; performing a secondary reaction, namely mixing the intermediate with formic acid to implement a reaction; adding a sodium hydroxide solution into the product of the secondary reaction till alkali; and performing filtering and drying, so as to obtain 2-amino-6-chloropurine. Raw materials are low in price and easy to obtain, reaction steps are small, the reaction time is short, a large amount of wastewater is not generated, and industrial production can be facilitated.
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Paragraph 0066; 0068; 0069; 0071; 0072; 0074
(2020/01/12)
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- Method for preparing 2-amino-6-chloropurine
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The invention provides a novel method for preparing 2-amino-6-chloropurine and aims to overcome the defects of a current 2-amino-6-chloropurine synthesizing process. The method includes the steps of firstly, using guanine as the raw material, adding an oxidizing agent, and performing oxidizing reaction to prepare a compound as shown in formula A; S2, adding the compound as shown in formula A intoa solvent, adding a chlorination agent, and performing chlorination reaction to obtain a compound as shown in formula B; S3, adding a reducing agent into the compound as shown in formula B, and performing reduction reaction to obtain a compound as shown in formula C, namely 2-amino-6-chloropurine. The method has the advantages that yield can be increased effectively, production cost can be lowered, operation steps can be simplified, and the method is safe and suitable for industrial production.
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Paragraph 0052; 0055; 0065; 0070; 0075
(2019/01/05)
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- Prolinamides of Aminouracils, Organocatalyst Modifiable by Complementary Modules
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We report the synthesis and evaluation of prolinamide organocatalysts that incorporate aminouracils. The features of these catalysts are enhanced NH acidity of the amide because of the electron-withdrawing nature of the heterocycle, an additional hydrogen-bond donor at the α or β positions of this functional group (using 6-aminouracil or 5,6-diaminouracil respectively), and it can be recovered due to its low solubility and used again without decreasing the enantioselectivity. A unique feature of these systems is the self-assembly capability with complementary modules by Watson–Crick interactions. These supramolecular adducts behave differently from the catalyst alone, some of them have lower performance but others improve the selectivity of the product. Therefore, this approach avoids the synthesis of many catalysts.
- Ruíz-Pérez, Karen M.,Quiroz-García, Beatriz,Hernández-Rodríguez, Marcos
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supporting information
p. 5763 - 5772
(2018/11/10)
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- Design, synthesis and evaluation of 4-aminoquinoline-purine hybrids as potential antiplasmodial agents
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A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P. falciparum with up to six-fold better activity (compound 10i, IC50: 0.08?μM) compared to the reference drug CQ (IC50: 0.5?μM) against the resistant strain. The synthesized compounds were also checked for their cytotoxicity towards mammalian cells and with the exception of two compounds out of the twenty synthesized hybrids, all others were non-cytotoxic up to 11.86?μM concentration. Mechanistic heme-binding studies were performed to identify the mechanism of action of the synthesized molecules and good binding interactions were observed. Computational docking studies showed that the most active hybrids dock well within the binding site of HGPRT protein. In silico ADME predictions of the most active hybrids showed that these compounds possess good pharmacokinetic behavior.
- Reddy, P. Linga,Khan, Shabana I.,Ponnan, Prija,Tripathi, Mohit,Rawat, Diwan S.
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p. 675 - 686
(2016/12/14)
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- Synthetic method for preparing high-purity 2-amino-6-chloroguanine
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The invention discloses a synthetic method for preparing high-purity 2-amino-6-chloroguanine. The synthetic method takes guanine shown in a formula (II) as a raw material which is subjected to a stirring reaction for 1-24h with a Vilsmeier reagent at 50-160 DEG C in an organic solvent to obtain a chloro-intermediate namely 2-formamido-6-chloroguanine shown in a formula (III), the chloro-intermediate shown in the formula (III) is hydrolyzed under the action of an aqueous solution of alkali, and then separation and purification are performed to obtain a high-purity product namely 2-amino-6-chloroguanine shown in a formula (I). According to the synthetic method disclosed by the invention, the intermediate generated in a reaction process is separated, and a hydrolysis reaction of the next step is carried out to obtain the high-purity product namely 2-amino-6-chloroguanine, wherein the purity reaches 99.0% or above via high-performance liquid chromatography (HPLC); the synthetic method disclosed by the invention is good in yield, low in production cost, mild in reaction condition, simple in operation, less in three wastes and environment-friendly, thereby having a great implementation value and great social and economic benefits.
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Paragraph 0011; 0016; 0018-0019 ; 0020-0039
(2017/11/18)
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- A nucleoside compound synthesis method (by machine translation)
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The invention relates to a method for synthesis of nucleoside compound, in particular of formula I and II shown in the preparation method of the compound, in the formula I and II, R1 And R2 Respectively is independently an hydroxy protecting group, preferably benzoyl, trityl, disubstituted phenyl, ethyl or tertiary butyl dimethyl silyl group; R3 And R4 Is alkyl (preferably C1 - C10 Alkyl, more preferably methyl, ethyl) or halogen (such as F, Cl or Br); B is the following arbitrary group wherein R5 Hydrogen or alkyl (preferably C1 - C10 Alkyl, more preferably methyl); X is hydroxyl or amino; Y is sulfur. (by machine translation)
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Paragraph 0063; 0064
(2017/08/27)
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- Facile synthesis of 8-azido-6-benzylaminopurine
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Bromination of 6-benzylaminopurine (1) with Br2 in AcOH in the presence of AcONa afforded 6-benzylamino-8-bromopurine (2) in 59% yield. The position of bromination was confirmed by direct transformation of bromide 2 by reaction with NaN3 in dimethyl sulfoxide to 8-azido-6-benzylaminopurine (3) in a yield of 70% and comparison of its properties with the known compound 2-azido-6- benzylaminopurine (11). Compounds 3 and 11 were checked for their biological activity in specific biotests based on the primary cytokinin effects in living plants. Both synthesized compounds displayed effects similar to the typical cytokinin 6-benzylaminopurine (1). Copyright Taylor and Francis Group, LLC.
- Steklov, Mikhail Yu.,Tararov, Vitali I.,Romanov, Georgy A.,Mikhailov, Sergey N.
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experimental part
p. 503 - 511
(2011/12/21)
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- Microwave assisted synthesis of 2,6-substituted aromatic-aminopurine derivatives
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A series of novel 2, 6-diaromatic-aminopurines (6a-6t) have been synthesized from guanine and characterized fully. The effects of different catalysts on the N-alkylation of 2-position of purine ring were discussed.
- Lu, Hong-Fei,Zhang, Liang-Ze,Wu, Ding-Ming,Zhou, Jun-Tao
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p. 1140 - 1144
(2011/11/04)
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- Synthesis and biological activities of O6-alkylguanine derivatives
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The synthesis of some biologically active O6-alkylguanine derivatives was achieved by alkoxylation of 2-amino-6-chloropurine with sodium alkoxides in polar aprotic solvent (DMSO) conditions. The starting material 2-amino-6-chloropurine was prepared by chlorination of 2,9-diacetylguanine (obtained from acetylation of commercially available guanine) by PEG-2000 phase transfer catalysis. The structures of the products were deduced from elemental analysis and spectral data (IR, 1H NMR, and mass spectra). All the title compounds were screened for their antifungal activities, and some of the compounds showed promising activities.
- Hu, Yu Lin,Ge, Qiang,Lu, Ming,Lu, Hong Fei
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experimental part
p. 425 - 432
(2012/01/13)
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- Synthesis of some biologically active halogenopurines
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A series of some biologically active halogenopurines were synthesized from commercially available guanine (1). The reaction of guanine with acetic anhydride yielded 2,9-diacetylguanine (2-1) by acetylation reaction. Further treatment of 2-1 with POCl3 by PEG-2000 phase transfer catalysis furnished the important compound 3a, then 2-amino-6-halogenopurines (3b-d) were obtained through chlorine-exchange halogenations between KX and 3a by TPPB phase transfer catalyst. Further, 2-halogenopurines (2-2a-d, 4-2a-d, 5a-d) were efficiently prepared from 2-amino-6-substituted purines (1, 3a, 4-1) via a diazotization catalyzed by their corresponding CuX, and some new compounds 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c and 5d have been discovered. The structures of synthesized compounds were mainly established on the basis of their elemental analysis, 1H NMR, as well as their mass spectral data. All the title compounds were screened for their antifungal activities, and some of the compounds showed promising activity.
- Hu, Yu Lin,Liu, Xiang,Lu, Ming,Ge, Qiang,Liu, Xiao Bin
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experimental part
p. 429 - 436
(2010/12/29)
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- Pharmaceuticals preparation of 2-amino-6-chloropurine with TEMAC
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A process for preparing a 2-amino-6-chloropurine or a 2-acylated derivative thereof, comprising reacting guanine or 2,9-diacylguanine with a chlorinating agent, in the presence of methyltriethylammonium chloride as phase transfer catalyst, and thereafter when necessary, removing the 9-acyl group by hydrolysis.
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- Double cone-like crystal form of 2-amino-6-chloropurine and preparation
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The present invention is directed to a method for preparing 2-amino-6-chloropurine having a double cone-like crystal form, comprising the steps of: (A) suspending 2-amino-6-chloropurine having an acicular or irregular-shaped crystal form in a liquid consisting essentially of water having a pH of from 3 to 10; and (B) heating the resulting suspension at a temperature of from 70° to 100° C. to complete the double cone-like crystal form conversion.
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- Process for preparing 2-amino-6-chloropurine
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The present invention relates to a new and improved process for preparing 2-amino-6-chloropurine comprising the step of reacting guanine in the presence of ammonium sulphate with hexamethyldisilazane. The process of this invention advantageously results in a high yield of 2-amino-6-chloropurine and may be carried out on a laboratory or an industrial scale.
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- 2-formylamino-6-halogenopurine
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The present invention is directed to a method for production of a 2-amino-6-halogenopurine, a novel synthesis intermediate therefor and a method for production of said synthesis intermediate. The desired 2-amino-6-halogenopurine is an intermediate for the production of compounds useful as antiviral agents, and by using the compound of the present invention as a starting material, the 2-amino-6-halogenopurine can be produced in high yield.
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- Process for preparing 2-amino-6-chloropurine
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A process for the preparation of the compound of formula (I): STR1 which process comprises reacting the compound of formula (II): STR2 with a chlorinating agent in the presence of a phase transfer catalyst containing chloride ions.
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