70258-18-3Relevant academic research and scientific papers
1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors
Dolbois, Aymeric,Bedi, Rajiv K.,Bochenkova, Elena,Müller, Anna,Moroz-Omori, Elena V.,Huang, Danzhi,Caflisch, Amedeo
, p. 12738 - 12760 (2021/09/13)
N6-methyladenosine (m6A) is the most frequent of the 160 RNA modifications reported so far. Accumulating evidence suggests that the METTL3/METTL14 protein complex, part of the m6A regulation machinery, is a key player in a variety of diseases including several types of cancer, type 2 diabetes, and viral infections. Here we report on a protein crystallography-based medicinal chemistry optimization of a METTL3 hit compound that has resulted in a 1400-fold potency improvement (IC50 of 5 nM for the lead compound 22 (UZH2) in a time-resolved F?rster resonance energy transfer (TR-FRET) assay). The series has favorable ADME properties as physicochemical characteristics were taken into account during hit optimization. UZH2 shows target engagement in cells and is able to reduce the m6A/A level of polyadenylated RNA in MOLM-13 (acute myeloid leukemia) and PC-3 (prostate cancer) cell lines.
Use of silicon compounds in cyclization reaction
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Paragraph 0054; 0099-0120, (2021/06/23)
The invention relates to the field of organic chemistry, and in particular, relates to an application of silicon compounds in cyclization reaction. On one hand, the invention provides a preparation method of 2-chloro-5-chloromethylpyridine, and the preparation method comprises the steps: carrying out cyclization reaction on 4-formyl-4,5-dichlorovaleronitrile in the presence of a silicon compound and an amide compound to provide the 2-chloro-5-chloromethylpyridine. On the other hand, the invention provides a preparation method of 5-chloromethyl-2-trifluoromethyl-1,3,4-oxadiazole, and the preparation method comprises the steps: carrying out cyclization reaction on 1-(chloracetyl)-2-(trifluoroacetyl)hydrazine in the presence of a silicon compound and an amide compound to provide the 5-chloromethyl-2-trifluoromethyl-1,3,4-oxadiazole. By using the silicon compound or/and amide provided by the invention as a cyclization reagent, cyclization synthesis can be efficiently carried out.
Method for continuously preparing 2-chloro-5-chloromethylpyridine by microchannel reactor
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Paragraph 0017-0026, (2019/04/17)
The invention discloses a method for continuously preparing 2-chloro-5-chloromethylpyridine by a microchannel reactor. The method includes the following steps: simultaneously injecting 2-chloro-5-methylpyridine and chlorine as raw materials into the microchannel reactor for chlorination, collecting a reaction product after the reaction, and crystallizing and distilling the reaction product to obtain the 2-chloro-5-chloromethylpyridine. The method has the advantages that the microchannel reactor is applied to carry out the reaction, the mixing uniformity is high, and the reaction time is greatly shortened; the inner diameter of a microchannel is small while the specific surface area thereof is large, reaction materials are instantaneously mixed uniformly in a precise ratio, the raw materialutilization rate and the product quality are improved, and the selectivity of the product is high, so that the productivity and purity of the product are improved while the production cost is lowered; in addition, the use of organic solvents is avoided in the preparation process, no waste polluting the environment is discharged in the production process, and environmental pollution and harm to the human body are reduced.
Method for preparing chloromethylpyridine 2- chloride -5. (by machine translation)
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Paragraph 0034; 0040-0186, (2019/12/29)
The mass percentage of, the precious metal in 2 - the precious metal catalyst of the noble metal 2 - catalyst of the " invention is that the mass percentage of 1%-10%; the noble 2 - metal 2 - in the precious metal; catalyst, 2 - containing the active, carbon or, aluminum oxide as the carrier is, the mass percent of the noble metal catalyst in the precious metal catalyst with the active carbon or alumina as the carrier 0.1%-0.5%; 2 - 2 - 82%, 98%, ". (by machine translation)
Green synthesis method of 2-chloro-5-chloromethylpyridine
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Paragraph 0007; 0018-0023, (2019/12/02)
The invention discloses a green synthesis method of 2-chloro-5-chloromethylpyridine. The green synthesis method comprises the following steps: dissolving CCC (2-chloro-2-chloromethyl-2-cyanobutyl aldehyde) and DMF (N,N-dimethylformamide) in a solvent, introducing phosgene to carry out a cyclization reaction, after the reaction is finished, blowing off unreacted phosgene with nitrogen, desolventizing, and carrying out reduced pressure distillation to obtain a brown liquid that is the product 2-chloro-5-chloromethylpyridine. By utilizing the synthesis method disclosed by the invention, zero wastewater discharge can be realized, the production cost is reduced, the synthesis process is simple, and the product yield is high.
Continuous synthesis technology of 2-chloro-5-chloromethylpyridine
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Paragraph 0043-0046; 0048; 0075; 0076; 0080-0082, (2018/11/04)
The invention provides a continuous synthesis technology of 2-chloro-5-chloromethylpyridine. The continuous synthesis technology comprises the following steps: under the action of a Vilsmeier reagent,propionaldehyde and a raw material A are subjected to a continuous cyclization reaction in a continuous synthesis reaction unit so as to obtain 2-chloro-5-methylpyridine, and 2-chloro-5-methylpyridine is continuously discharged and continuously conveyed into a chlorination unit, wherein the raw material A is selected from acetonitrile and/or acetamide; and in the chlorination unit, 2-chloro-5-methylpyridine and chlorine are subjected to a chlorination reaction to obtain 2-chloro-5-chloromethylpyridine. By the adoption of the continuous synthesis technology, reaction rate is raised, generationof by-products is reduced, and stability and safety of the synthesis process are also enhanced. In comparison with a batch synthesis technology, the invention has the following beneficial effects: bythe continuous process in the chlorination process, the risks that chlorine introduction speed is too fast, cooling is insufficient, cooling is interrupted, reaction heat is too late to move away, reaction is out of control and the like are reduced.
Synthesis method of 2-chloro-5-chloromethylpyridine
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Paragraph 0019; 0020; 0021; 0023; 0024; 0025, (2018/04/03)
The invention discloses a synthesis method of 2-chloro-5-chloromethylpyridine. The synthesis method comprises the following main steps: 1, using 3-methylpyridine (I) as a main starting material and water as a reaction medium, performing a complete reaction on the 3-methylpyridine (I) and chlorine gas at 40-60 DEG C in the presence of a catalyst, and post-treating to obtain 2-chloro-5-methylpyridine (II) as a reaction raw material in the next step; 2, using the 2-chloro-5-methylpyridine (II) as the reaction raw material, in the presence or absence of a reaction medium, performing a complete reaction on the 2-chloro-5-methylpyridine (II) and the chlorine gas at 50-60 DEG C in the presence of the catalyst, and post-treating to obtain 2-chloro-5-chloromethylpyridine with the purity being higher than or equal to 99%. A reaction equation is as shown in the description. The method disclosed by the invention has the advantages of high reaction selectivity, stable product quality, simple production operation, increase in raw material utilization rate through combined use of the raw materials, reduction in production cost, and the like.
A 2 - chloro - 5 - chloromethyl pyridine production method (by machine translation)
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Paragraph 0022; 0023; 0024, (2018/04/03)
The invention discloses a 2 - chloro - 5 - chloromethyl pyridine production method, characterized in that respectively will be 2 - chloro - 5 - chloromethyl - 4 - cyano-butyraldehyde and CCl3 )2 CO3 In the dissolved in a certain amount of solvent, and then the two solution preheating to 100 °C -110 °C after, entering in the reactor according to the rate of the reaction, the material level in the reactor at a 250 - 300 seconds, overflow to the two-stage reactor, 105 °C -110 °C reaction 300 - 430 seconds, overflow to hydrolysis in the kettle, in and after the hydrolysis, desolvation and distillation, to obtain 2 - chloro - 5 - chloromethyl pyridine. (by machine translation)
Synthesis method of 2-chloro-5-chloromethyl pyridine
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Paragraph 0023; 0027; 0029; 0031; 0036; 0041; 0043, (2018/04/02)
The invention discloses a synthesis method of 2-chloro-5-chloromethyl pyridine. After 3-methylpyridine is vaporized, nitrogen is taken as carrier gas and mixed with chlorine, mixed gas is introduced into a tubular reactor containing a supported palladium chloride catalyst for a chlorination reaction, and 2-chloro-5-chloromethyl pyridine is obtained. 3-methylpyridine and chlorine are taken as raw materials, the supported palladium chloride catalyst is used, and 2-chloro-5-chloromethyl pyridine is obtained through a one-step reaction. The reaction speed can be increased, the target product selectivity is advantageously improved, and the molar yield of 2-chloro-5-chloromethyl pyridine reaches about 50%. Few three wastes are produced during reaction, precious metal palladium used during the reaction is easy to recover, and the comprehensive cost is lower.
Synthetic method of acetamiprid
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Paragraph 0012; 0013; 0014; 0015; 0016; 0017; 0018-0020, (2017/07/21)
The invention relates to a synthetic method of acetamiprid. The synthetic method is implemented according to the following steps: acetamiprid intermediate 2-chloro-5-chloromethylpyridine is prepared from toluene as a solvent, 2-chloro-2-chloromethyl-4-cyanobutyraldehyde as a starting material and triphosgene as a chlorination agent at 45-60 DEG C, and then an acetamiprid technical is synthesized through ammoniation and esterification. The reaction system is simple, few side reactions are contained, the raw materials are clean and easily available, few reaction steps are adopted, the operation is convenient, the yield is high, and the quality is stable.
