107512-34-5Relevant academic research and scientific papers
Purification synthesis method of 2-methyl-3-methoxy-4-chloropyridine
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Paragraph 0029-0031; 0032-0035; 0036-0041; 0042-0048, (2020/12/08)
The invention discloses a purification synthesis method of 2-methyl-3-methoxy-4-chloropyridine. The method comprises the following steps: carrying out low-temperature crystallization purification on raw material 2-methyl-3-methoxy-4H-pyridine to remove organic impurities in raw material B2, thereby reducing the content of side reaction substances in the chlorination reaction; and side reactions such as decomposition and degradation of a reaction product are reduced through an improved mode of rapidly distilling a chlorination liquid and an extraction liquid, so that the yield is increased, theconsumption and three wastes are reduced, and a remarkable effect is achieved. The improved process is convenient to operate, mild in reaction condition, safe, reliable, high in product yield and lowin cost.
Synthesis method of 2-methyl-3-methoxy-4-chloropyridine
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Paragraph 0035-0047, (2020/12/15)
The invention discloses a synthetic method of 2-methyl 3-methoxy 4-chloropyridine. Triphosgene is used to replace phosphorus oxychloride to perform chlorination reaction; organic base is adopted to perform catalytic reaction, and byproduct phosgene at low temperature is recovered through a solvent in the process; and therefore, the purposes of high-efficiency reaction, pollution reduction, raw material utilization ratio increase and the like can be achieved. The method has the advantages of obvious cost reduction, safety improvement and environmental protection, so the method improves the yield, reduces the consumption, three wastes and the cost, and is very suitable for industrial production.
Preparation method of 2-methyl-3-methoxyl-4-chloropyridine
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Paragraph 0025-0059, (2018/05/16)
The invention discloses a preparation method of 2-methyl-3-methoxyl-4-chloropyridine. The preparation method comprises the following steps: adding 10 to 15 kg of 2-methyl-3-methoxyl-4H-pyridine into 50 to 75 kg of dichloroethane, and heating to dissolve the mixture; slowly adding 12 to 18 kg of phosphorus oxychloride into the solution under stirring; then performing heat preservation at 80 to 85 DEG C for 10 to 12 hours; performing reduced pressure distillation to recycle dichloroethane, cooling the material solution obtained by the reduced pressure distillation to 18 to 22 DEG C, and slowly adding the material solution into iced water for uniform stirring for hydrolysis; cooling the hydrolyzed material solution to 0 to 10 DEG C, adding an alkaline solution to adjust the pH of the materialsolution to 7 to 9, pouring the solution into a separating funnel for stewing for 1 to 2 hours, then collecting a lower-layer oily matter, extracting upper-layer liquid with an extractant, putting the extracted liquid into the collected oily matter, adding anhydrous sodium sulfate, performing drying and suction filtration, and performing reduced pressure evaporation to remove the extractant, thusobtaining the 2-methyl-3-methoxyl-4-chloropyridine. The preparation method is mild in reaction condition, convenient in technological operation, safe, reliable, high in product yield and low in cost.
A 4-chloro-3-methoxy-2-methyl-4-pyridine synthesis method
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Paragraph 0034; 0035, (2017/02/24)
The invention discloses a synthesis method of 4-chloro-3-methoxy-2-methyl-4-pyridine. The synthesis method comprises the following steps of carrying out addition reaction on 3-methoxy-2-methyl-4-pyranone and excessive phosphorus oxychloride, wherein the 3-methoxy-2-methyl-4-pyranone is used as a main starting material; absorbing the excessive phosphorus oxychloride in the reaction system using DMF (Dimethyl Formamide) after the addition reaction is finished to obtain a Vilsmeier agent; hydrolyzing the rest intermediate in ice water by layering to obtain the product of 4-chloro-3-methoxy-2-methyl-4-pyridine. The synthesis method disclosed by the invention is novel in process; and the excessive phosphorus oxychloride in the system is treated by using the DMF to obtain side products of the Vilsmeier reagent to greatly reduce the generation of acid liquor wastewater and simultaneously to improve the yield of the product. The synthesis method disclosed by the invention is mild in reaction conditions, simple in process operation, green, environment-friendly, low in cost and high in yield.
Synthesis of a DOTA (Gd3+)-conjugate of proton-pump inhibitor pantoprazole for gastric wall imaging studies
Maharvi, Ghulam M.,Bharucha, Adil E.,Fauq, Abdul H.
supporting information, p. 2808 - 2811 (2013/06/27)
Magnetic resonance imaging (MRI) is used to evaluate gastrointestinal (GI) structure and functions in humans. Despite filling the viscus lumen with a contrast agent, visualization of the viscus wall is limited. To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd-based MRI contrast agent, encaged with a chelating agent (DOTA), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon. The DOTA linkage was installed at a mechanism-based strategic location in the pantoprazole molecule to minimize a possible negative effect of the structural modification on the drug. It is anticipated that by defining the wall of the stomach and colon, this compound will facilitate functional MRI of the GI tract in humans.
Antimicrobial 2-pyridones, their compositions and uses
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, (2008/06/13)
Compounds having the general structure: are effective antimicrobial agents.
Structure-activity relationship of omeprazole and analogues as Helicobacter pylori urease inhibitors
Kuhler,Fryklund,Bergman,Weilitz,Lee,Larsson
, p. 4906 - 4916 (2007/10/03)
Helicobacter pylori urease belongs to a family of highly conserved urea- hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K+-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K+- ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pK(a)-value of the pyridine, the pK(a)-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of β- mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 μmol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 μmol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.
(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate
Kohl,Sturm,Senn-Bilfinger,Simon,Kruger,Schaefer,Rainer,Figala,Klemm
, p. 1049 - 1057 (2007/10/02)
[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.
SYNTHESES OF A NATURALLY OCCURRING HYDROXAMIC ACID AND ITS ANALOGUES
Ohta, Akihiro,Takahashi, Nobuhiro,Shirokoma, Yasuko
, p. 875 - 884 (2007/10/02)
A naturally occurring cyclic hydroxamic acid, isolated from Pseudomonas species, and its analogues were synthesized via six steps starting from 2-hydroxy-3-methoxypyridine.The antimicrobial activity of the synthesized compounds is described.
