- Micro-reaction system and method for continuously preparing 2-methyl-4-amino-5-aminomethylpyrimidine by using same
-
The invention belongs to the technical field of pharmaceutical engineering, and particularly relates to a micro-reaction system and a method for continuously preparing 2-methyl-4-amino-5-aminomethylpyrimidine by using the micro-reaction system. The method comprises the following steps: modifying a Raney nickel catalyst by using formalin, filling a micro-channel reactor with the modified Raney nickel catalyst; simultaneously conveying hydrogen and a substrate solution containing both 2-methyl-4-amino-5-cyanopyrimidine and an alkaline agent into the micro-reaction system comprising a micro-mixerand the micro-channel reactor which communicate with each other in sequence; and carrying out a continuous catalytic hydrogenation reaction to obtain the 2-methyl-4-amino-5-aminomethylpyrimidine. Compared with the prior art, the method provided by the invention has the advantages that reaction time is only several minutes, the yield of the product 2-methyl-4-amino-5-aminomethylpyrimidine is greater than 99%, a technological process is continuous, an automation degree is high, space-time yield is high, operation is simple and convenient, the separation steps of reaction liquid and a catalyst is not needed, cost is low, and industrial production is easy.
- -
-
Paragraph 0023-0055
(2021/02/10)
-
- Fully Continuous Flow Synthesis of 5-(Aminomethyl)-2-methylpyrimidin-4-amine: A Key Intermediate of Vitamin B1
-
Herein, we demonstrate an expeditiously fully continuous flow synthesis of 5-(aminomethyl)-2-methylpyrimidin-4-amine, a key intermediate for vitamin B1. The process is accomplished via three chemical transformations in six sequential continuous flow devices from an economical starting material, 2-cyanoacetamide. First, single step continuous flow synthesis is demonstrated in a certain type of flow reactor for each reaction step, with a yield of 94, 90, and 99%, respectively. Then, fully continuous flow synthesis of 5-(aminomethyl)-2-methylpyrimidin-4-amine is demonstrated in 84% total yield with a total residence time of 74 min and 0.92 g/h throughput.
- Chen, Fener,Huang, Huashan,Jiang, Meifen,Liu, Minjie
-
p. 2331 - 2337
(2021/10/25)
-
- Fully continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine
-
The invention discloses a fully continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine. The method comprises the following steps: mixing a mixed solution of cyanoacetamide, N, N-dimethylformamide and a catalyst with phosphorus oxychloride in a micro-mixer, and carrying out a continuous flow reaction in a micro-channel reactor to obtain (dimethyl aminomethylene) malononitrile; continuously quenching, continuously extracting and separating, concentrating an organic solution, mixing with a methanol solution, and continuously reacting with organic alkali to obtain 2-methyl-4-amino-5-cyanopyrimidine; continuously filtering the reaction mixed solution, dissolving the solid with methanol, conveying the dissolved solid and hydrogen to a fixed bed microchannel reactor through a micromixer, carrying out hydrogenation reaction, and concentrating, drying and purifying the product to obtain the 2-methyl-4-amino-5-aminomethylpyrimidine product. The method is mild in reaction condition, short in reaction time, high in product yield, low in energy consumption, green, safe and easy to industrially amplify and apply.
- -
-
Paragraph 0006; 0045; 0047-0061
(2021/07/17)
-
- Preparation process of 2-methyl-4-amino-5-pyrimidinemethanamine
-
The invention discloses a preparation process of 2-methyl-4-amino-5-pyrimidinemethanamine. The preparation process of 2-methyl-4-amino-5-pyrimidinemethanamine comprises the following steps: 1) adding27-30 parts of DMF and 48-51 parts of dimethyl sulfate in a four-necked flask, heating to the temperature of 60-90 DEG C, insulating and stirring for 3-6 h, and then cooling; 2) adding 48-51 parts ofa methanol solution of sodium methylate, and after dropwise adding is finished, insulating and stirring for 5-15 min; 3) adding 27-30 parts of 3-aminopropionitrile, stirring for 30-60 min, and distilling under reduced pressure to obtain an intermediate 1; 4) then adding 130-150 parts of dichloromethane and stirring for 10-30 min, filtering, and distilling under reduced pressure to obtain an intermediate 2; and 5) adding 74-77 parts of a methanol solution of sodium methylate in the four-necked flask, cooling to the temperature of minus 5-5 DEG C, slowly adding 38-41 parts of acetamidine hydrochloride, insulating and stirring for 20-40 min, filtering, transferring to another flask and adding the intermediate 2 and 38-41 parts of NaOH, and stirring for 12-18 h after heating to obtain the final product. The preparation process of 2-methyl-4-amino-5-pyrimidinemethanamine is simple, and is low in pollution and low in raw material cost, and the yield of the product reaches up to 92.5%.
- -
-
Paragraph 0016-0036
(2019/02/13)
-
- 2-methyl-4-amino-5 - (aminomethyl) method for the preparation of pyrimidine
-
The invention discloses a preparation method of 2-methyl-4-amino-5-(aminomethyl) pyrimidine. The preparation method is characterized by comprising the following steps: in the presence of an alkaline agent, contacting 2-methyl-4-amino-5-(formamide methyl) pyrimidine with methanol to react, wherein the weight ratio of the amount of the alkaline agent to the amount of the 2-methyl-4-amino-5-(formamide methyl) pyrimidine is (0.001-0.05) to 1. According to the method provided by the invention, a great deal of organic salts, inorganic salts and liquid waste are not produced, and byproducts as well as the residual methanol can be completely recycled. The preparation method is economical, environmentally friendly and capable of meeting the development requirements of the existing national energy-saving environmental-protection industrial economy. Besides, the preparation method provided by the invention is simple to operate, easily available in raw material and suitable for the requirements of the industrial production. Moreover, the product is easy to separate and purify.
- -
-
Paragraph 0031-0032
(2017/03/14)
-
- One-step ring preparation of 2-methyl-4-amino-5-amino methyl pyrimidine convenient synthetic method
-
The invention relates to a portable synthesis method for preparing 2-methyl-4-amino-5-aminoethylpyrimidine through one-step cyclization reaction. The method comprises the following steps: directly catalyzing acetamidine hydrochloride and 3-acyl aminopropionitrile to condense and to react with triester orthoformate for dealcoholization and cyclization by using lewis acid, and then hydrolyzing to obtain a vitamin B1 key intermediate, namely the 2-methyl-4-amino-5-aminoethylpyrimidine. According to the method disclosed by the invention, the raw materials are low in cost and easily obtained, and no sodium alcoholate needs to be used for dissociating acetamidine hydrochloride, thus the decomposition of acetamidine is reduced, and the high yield is achieved through reaction; the cyclization and hydrolysis reactions are sequentially carried out, products in all steps are not required to be separated and purified, and the synthesis method is simple and convenient to operate. Highly carcinogenic o-chloroaniline or other micromolecular aniline compounds are not used, and the portable synthesis method is environment-friendly in process, free of production of wastewater and beneficial to industrial production.
- -
-
Paragraph 0045; 0046; 0051
(2017/03/08)
-
- Vitamin B1 key intermediate 2-methyl-4-amino-5-amino methyl pyrimidine method for preparing environmental protection of
-
The invention relates to an environment-friendly preparation method for a key intermediate 2-methyl-4-amino-5-aminomethyl pyrimidine of vitamin B1. The method comprises the following steps: substituting highly oncogenic o-chloroaniline or other micromolecular aniline derivatives with a functional polymer containing an aromatic amine structural unit; carrying out a condensation reaction with enol alkali under an acidic condition so as to produce a corresponding enamine polymer; subjecting the enamine polymer and ethanamidine hydrochloride to condensation so as to produce 2-methyl-4-amino-5-formylamino-pyrimidine; and carrying out hydrolysis so as to prepare 2-methyl-4-amino-5-aminomethyl pyrimidine; wherein the functional polymer containing the aromatic amine structural unit is released at the same time and is cyclically used for next batch of reactions. The method has short process flow, discharges a small amount of waste water and waste liquid and is beneficial for industrial production and for improvement of the industrial production level of vitamin B1.
- -
-
Paragraph 0108; 0134; 0135; 0145
(2016/10/31)
-
- Design, synthesis and molecular docking of amide and urea derivatives as Escherichia coli PDHc-E1 inhibitors
-
By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.
- He, Jun-Bo,Ren, Yan-Liang,Sun, Qiu-Shuang,You, Ge-Yun,Zhang, Li,Zou, Peng,Feng, Ling-Ling,Wan, Jian,He, Hong-Wu
-
p. 3180 - 3186
(2014/06/09)
-
- Lewis acid-catalyzed synthesis of 4-aminopyrimidines: A scalable industrial process
-
Pyrimidine synthesis starting from acrylonitrile has been known since the 1960s. The new Lewis acid-catalyzed condensation reaction allows the synthesis of 4-aminopyrimidines starting from the easily accessible chemical acrylonitrile without the need for carcinogenic chemicals and costly derivatization in up to 90% yield. The method is versatile and applicable for industrial-scale synthesis of biologically relevant substances such as vitamin B1 and trimethoprim.
- Letinois, Ulla,Schuetz, Jan,Haerter, Ralph,Stoll, Rinke,Huffschmidt, Florian,Bonrath, Werner,Karge, Reinhard
-
supporting information
p. 427 - 431
(2013/05/09)
-
- METHODS OF LOWERING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)
-
The invention relates to new methods of modulating cholesterol by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) with fatty acid derivatives; and new methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid derivative. The present invention is also directed to fatty acid bioative derivatives and their use in the treatment of metabolic diseases.
- -
-
Paragraph 0267
(2014/01/07)
-
- Development of two scalable syntheses of 4-amino-5-aminomethyl-2- methylpyrimidine: Key intermediate for vitamin b1
-
Two scalable processes for the synthesis of 4-amino-5-aminomethyl-2- methylpyrimidine (2) are described. In the first approach, the less expensive 2-cyanoacetamide was reacted with Vilsmeier reagent to afford enamine 18, followed by the condensation with acetamidine to produce the 4-amino-2-methylpyrimidine-5-carbonitrile (6); subsequent hydrogenation gave 2 in 65% overall yield. In the second approach, malononitrile was treated with the ionic salt 21, prepared in situ from DMF and dimethyl sulfate, to give 18, which, without isolation was reacted with acetamidine hydrochloride to afford the common intermediate 6. Overall yield of this approach was 70%. Both methods are performed in a convenient manner suitable for industrial use.
- Zhao, Lei,Ma, Xiao-Dong,Chen, Fen-Er
-
experimental part
p. 57 - 60
(2012/05/31)
-
- PROCESS FOR THE MANUFACTURE OF A PRECURSOR OF VITAMIN B1
-
The present invention relates to a novel process for the manufacture of Grewe-diamine comprising the following step: hydrolyzing a compound of formula (II), wherein R is hydrogen or straight- or branched chain C1-4 alkyl, with an aqueous alkali or alkaline-earth metal hydroxide solution, characterized in that the hydrolysis is carried out in the presence of an organic solvent.
- -
-
Page/Page column 11; 19-20; 24
(2008/06/13)
-
- 3-deoxyglucosone and skin
-
The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.
- -
-
-
- Preparation of 2-methyl-4-amino-5-aminomethylpyrimidine
-
2-Methyl-4-amino-5-aminomethylpyrimidine of the formula 1 is prepared by reacting 2-methyl-4-amino-5-alkoxymethylpyrimidine of the formula 2 where R=C1-C6-alkyl, with ammonia in the presence of a catalyst.
- -
-
-
- Amino-substituted pyrimidines, derivatives and methods of use therefor
-
The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
- -
-
-
- 2-Alkyl-4-amino-5-aminomethylpyrimidines
-
A novel 2-lower alkyl-4-amino-5-substituted iminopyrimidine compound represented by the formula: STR1 wherein R is a lower alkyl, and Y is hydroxyl or amino which may be protected or a salt thereof is obtainable by allowing a formylpyrimidine compound represented by the formula: STR2 wherein R is a lower alkyl to react with a compound represented by the formula H2 N--Y, wherein Y is hydroxyl or amino which may be protected, or a salts thereof. The iminopyrimidine compound gives the known pyrimidine compound represented by the formula: STR3 wherein R is as defined above in high yield. Therefor, the process is very useful as an industrial production method.
- -
-
-
- Process for the preparation of a 2-alkyl-4-amino-5-aminomethylpyrimidine
-
There is disclosed a process for the preparation of a 2-alkyl-4-amino-5-aminomethylpyrimidine, which comprises subjecting a 2-alkyl-4-amino-5-formylpyrimidine to catalytic reaction with hydrogen and ammonia in the presence of a reduction catalyst. According to the process of this invention, the desired product can be obtained in much higher yield as compared with the processes known to the art.
- -
-
-
- Process for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine
-
Disclosed is a process for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine comprising (i) a first step of reacting 2-alkyl-4-amino-5-formylpyrimidine with ammonia in an inert solvent in the presence of at least one compound selected from heteropolyacids, isopolyacids, oxyacids and salts thereof containing molybdenum or tungsten, and (ii) a second step of reacting the reaction product in the first step catalytically with ammonia and hydrogen in an inert solvent in the presence of a reducing catalyst together with or without a hydroxide of an alkali metal or alkaline earth metal.
- -
-
-
