698-29-3Relevant articles and documents
Studies on the Thorpe-Ziegler-reaction. A new synthesis of the pyridine part of thiamine
Edenhofer,Spiegelberg,Oberhaensli
, p. 1230 - 1240 (1975)
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Fully continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine
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Paragraph 0006; 0045-0046; 0048-0061, (2021/07/17)
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.
Fully Continuous Flow Synthesis of 5-(Aminomethyl)-2-methylpyrimidin-4-amine: A Key Intermediate of Vitamin B1
Chen, Fener,Huang, Huashan,Jiang, Meifen,Liu, Minjie
, p. 2331 - 2337 (2021/10/25)
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.
Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
, p. 5652 - 5661 (2017/10/09)
By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.