2516-96-3Relevant articles and documents
Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow**
Sagmeister, Peter,Lebl, René,Castillo, Ismael,Rehrl, Jakob,Kruisz, Julia,Sipek, Martin,Horn, Martin,Sacher, Stephan,Cantillo, David,Williams, Jason D.,Kappe, C. Oliver
, p. 8139 - 8148 (2021)
In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and UHPLC) in the multistep synthesis of an active pharmaceutical ingredient, mesalazine. This synthetic route exploits flow processing for nitration, high temperature hydrolysis and hydrogenation reactions, as well as three inline separations. Advanced data analysis models were developed (indirect hard modeling, deep learning and partial least squares regression), to quantify the desired products, intermediates and impurities in real time, at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating both steady state and dynamic experiments and represents a significant step forward in data-driven continuous flow synthesis.
Synthesis method for (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone
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Paragraph 0037; 0038, (2017/07/12)
The invention discloses a synthesis method for (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone. According to the method, with cheap o-chlorobenzoic acid as a starting material, (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone is obtained by nitration, Friedel-Crafts acylation and reduction and finally by Sandmeyer reaction for iodination. The materials used by the method are cheap and easy to obtain, and the method adopting Sandmeyer reaction for iodination can increase the iodine utilization rate, and has the characteristics of simplicity in operation, high yield, high purity and suitability for industrialized production. (The chemical formula is shown in the specification).
Preparation method for 2-chloro-5-iodobenzoic acid
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Paragraph 0027; 0028, (2017/07/21)
The invention discloses a preparation method for 2-chloro-5-iodobenzoic acid. The preparation method is characterized in that cheap o-chlorobenzoic acid is taken as a starting material to obtain 2-chloro-5-iodobenzoic acid through nitration, reduction and diazotization iodination. The method shortens reaction steps, increases the yield and is suitable for industrial production.
Method for synthesizing 2-chloro-5-nitrobenzoic acid through microchannel reactor
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Paragraph 0044-0047, (2017/08/29)
The invention provides a method for synthesizing 2-chloro-5-nitrobenzoic acid through a microchannel reactor. The method comprises the steps of dissolving a raw material o-chlorobenzoic acid into concentrated sulfuric acid to obtain a material 1, and entering a preheating module; adopting fuming nitric acid and the concentrated sulfuric acid as a material 2 and a material 3, and entering another preheating module; preheating the material 1, the material 2 and the material 3, entering a reaction module group for reacting, collecting effluent reaction liquid, processing to obtain a crude product, and refining to obtain the product 2-chloro-5-nitrobenzoic acid. According to the method provided by the invention, the reaction time is shortened to a few minutes to a few seconds, the production energy consumption is reduced, and the reaction efficiency is remarkably improved. High-efficient mass and heat transfer efficiency ensures the reaction temperature to maintain within a setting range, the possibilities of temperature out of control, temperature runaway and even sharp reaction overflow or explosion caused by over-high local concentration do not exist, the intrinsic safety problem of the nitration reaction is solved fundamentally, and the reaction yield and the product purity are remarkably improved.
Preparation method of 2-chloride-5-nitrobenzoic acid
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Paragraph 0013; 0016, (2017/08/27)
The invention provides a preparation method of 2-chloride-5-nitrobenzoic acid. The preparation method comprises the following steps: mixing concentrated nitric acid and fuming sulphuric acid with the SO3 concentration of 20 percent according to the mass ratio of 1:(2-3), and controlling the temperature of the solution to be less than 10 DEG C in a mixing process; dripping 2-chloride trichlorotoluene, controlling the temperature of reaction liquid to be 0 to 10 DEG C, and continuously stirring at the end of dripping till the reaction is completed; pouring the reaction liquid into ice water, extracting with dichloromethane, washing an organic phase with a saturated sodium bicarbonate solution, and concentrating and drying to obtain 2-chloride-5-nitro trichlorotoluene; preparing concentrated sulfuric acid with the concentration of 85 weight percent, heating to 60 to 65 DEG C, adding the 2-chloride-5-nitro trichlorotoluene in batches, and preserving the heat till the reaction is completed; cooling the reaction liquid, adding water into the reaction liquid for dilution, extracting with ethyl acetate, taking an organic phase, and performing washing and concentration to obtain 2-chloride-5-nitrobenzoic acid. The technological steps are more reasonable in design and high in operability; the number of byproducts is small; the prepared product is relatively high in purity and can meet the requirement on industrial application.
Design, synthesis and biological evaluation of 3-substituted indenoisoquinoline derivatives as topoisomerase I inhibitors
Zhao, Qian,Xu, Xi,Xie, Zhouling,Liu, Xiao,You, Qidong,Guo, Qinglong,Zhong, Yi,Li, Zhiyu
supporting information, p. 1068 - 1072 (2016/05/24)
A new series of indenoisoquinoline derivatives was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in HepG2, A549 and HCT-116 cell lines. Compounds 9a, 9b, 10a, 10c, 10e, 18a and 18b manifested potent inhibitory activity against the three tested cancer cell lines. Nineteen compounds were also tested for Top I inhibition at 50 μM. Almost all the tested compounds showed potent Top I inhibition activity at this concentration. The most potent compounds 9a and 10a demonstrated more cytotoxicity than HCPT and TPT and was comparable to CPT in inhibitory activities on Top I in our biological assay.
Method and compositions for identifying anti-HIV therapeutic compounds
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, (2008/06/13)
Methods are provided for identifying anti-HIV therapeutic compounds substituted with carboxyl ester or phosphonate ester groups. Libraries of such compounds are screened optionally using the novel enzyme GS-7340 Ester Hydrolase. Compositions and methods relating to GS-7340 Ester Hydrolase also are provided.
Method and compositions for identifying anti-HIV therapeutic compounds
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, (2008/06/13)
Methods are provided for identifying anti-HIV therapeutic compounds substituted with carboxyl ester or phosphonate ester groups. Libraries of such compounds are screened optionally using the novel enzyme GS-7340 Ester Hydrolase. Compositions and methods relating to GS-7340 Ester Hydrolase also are provided.
N-arylmethylthioanilide compounds useful for the inhibition of the replication of HIV
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, (2008/06/13)
Compounds of the formula STR1 wherein A and X are independently oxygen or sulphur; R6 is H, halogen, alkyl, alkoxy, alkylthio, cyano, or nitro; Y is --CH2 O--, --OCH2 --, --CH2 S--, or --CH2 SO2 --; Q is a substituted or unsubstituted phenyl or aromatic heterocyclic group: useful for the inhibition of the replication of HIV-1, in vitro and in vivo.
Nitromethyl ketones, process for preparing them and compositions containing them
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, (2008/06/13)
The present invention relates to the compounds of formula: STR1 in which R1, R2, R3, E, A, X, Z, p and n are as defined herein. These compounds are aldose reductase inhibitors.
