67476-67-9Relevant academic research and scientific papers
One-pot synthesis method for synthesizing 2-hydroxy-5-nitropyridine
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Paragraph 0027-0031, (2021/05/05)
The invention discloses a one-pot synthesis method for synthesizing 2-hydroxy-5-nitropyridine. The method comprises the following specific reaction steps: adding 2-aminopyridine into concentrated sulfuric acid in batches, controlling the temperature at 10-20 DEG C, adding concentrated nitric acid, keeping the temperature at 40-50 DEG C, and stirring; after nitration is completed, adding reaction liquid into water for quenching, controlling the temperature to be 0-10 DEG C, dropwise adding a sodium nitrite aqueous solution, and carrying out diazo reaction; adding a proper amount of ammonia water to adjust the acid concentration; and filtering the solution after the acid concentration is adjusted, and drying a filter cake to obtain the product. The invention provides a novel preparation method of 2-hydroxy-5-nitropyridine. The method has the advantages that the post-treatment is simple, isomers are separated by utilizing the concentration of acid, and the isomers generated by nitration reaction do not need to be independently purified, the nitration reaction and the diazotization reaction are continuously operated, and thus the waste water generated in the amplified production is greatly reduced, and the production cost is saved; the preparation method is never reported in literatures, is a brand-new preparation method of the 2-hydroxy-5-nitropyridine, and provides a new synthesis thought for similar compounds of the 2-hydroxy-5-nitropyridine.
Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice
Wang, Weisi,Yao, Junmin,Chen, Zhuo,Sun, Yiming,Shi, Yuqing,Wei, Yufen,Zhou, Hejun,Yu, Yingfang,Li, Shizhu,Duan, Liping
supporting information, p. 5569 - 5579 (2020/11/03)
Background and Purpose: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy. Experimental Approach: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed. Key Results: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg?1·day?1) and cured the established infection (CD50 = 10.13 mg·kg?1·day?1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg?1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg?1). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice. Conclusion and Implications: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.
Preparation method of 2-amino substituted six-membered nitrogen-containing heterocycle complex
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Paragraph 0025; 0026; 0103, (2019/02/08)
The invention discloses a preparation method of a 2-amino substituted six-membered nitrogen-containing heterocycle complex. The preparation method comprises the following steps: mix 2-fluorine substituted six-membered nitrogen-containing heterocycle complex and amidine hydrochloride salt compound, and then react under the action of a alkaline substance to obtain a 2-amino substituted six-memberednitrogen-containing heterocycle complex. Preferably, the 2-amino substituted six-membered nitrogen-containing heterocycle complex is a 2-amino pyridine compound, a 2-aminopyrimidine compound or a 2-aminopyrazine compound. Compared with the prior art, the method has the advantages of simple synthesis conditions, less reaction steps, mild reaction conditions, low cost of the catalyst used, less waste discharge and good functional group tolerance.
Transition-metal-free access to 2-aminopyridine derivatives from 2-fluoropyridine and acetamidine hydrochloride
Li, Yibiao,Huang, Shuo,Liao, Chunshu,Shao, Yan,Chen, Lu
supporting information, p. 7564 - 7567 (2018/11/02)
Under catalyst-free conditions, an efficient method for the synthesis of 2-aminopyridine derivatives through the nucleophilic substitution and hydrolysis of 2-fluoropyridine and acetamidine hydrochloride has been developed. This amination uses inexpensive acetamidine hydrochloride as the ammonia source and has the advantages of a high yield, high chemoselectivity and wide substrate adaptability. The results suggest that other N-heterocycles containing fluorine substituents can also complete the reaction via these reaction conditions and yield the target products.
Synthesis of Amides by Nucleophilic Substitution of Hydrogen in 3-Nitropyridine
Amangasieva,Borovlev,Demidov,Avakyan,Borovleva
, p. 867 - 872 (2018/07/31)
3-Nitropyridine reacted with nitrogen-centered carboxylic acid amide anions in anhydrous DMSO in the presence of K3Fe(CN)6 via oxidative nucleophilic substitution of hydrogen to give previously unknown N-(5-nitropyridin-2-yl) carboxa
PROCESS FOR THE CATALYTIC DIRECTED CLEAVAGE OF AMIDE-CONTAINING COMPOUNDS
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Page/Page column 51; 53, (2017/04/11)
The present invention relates to a catalytic method for the conversion of amide-containing compouds by means of a build-in directing group and upon the action of a heteronucleophilic compound (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or a thiol (RSH)) in the presence of a metal catalyst to respectively esters, thioesters, carbonates, thiocarbonates and to what is defined as amide-containing compounds (such as carboxamides, urea, carbamates, thiocarbamates). The present invention also relates to these amide-containing compounds having a build-in directing group (DG), as well as the use of such directing groups in the catalytic directed cleavage of N-DG amides with the use of heteronucleophiles (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or thiol (RSH)).
5 - nitro - 2 - aminopyridine preparation method
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Paragraph 0035; 0036; 0037; 0041-0087; 0090-0104, (2017/07/11)
The invention discloses a preparation method of 5-nitro-2-aminopyridine. The preparation method comprises the following steps: S1, preparing a reaction liquid I, namely adding an organic solvent to a 2-aminopyridine solution and mixing to obtain the reaction liquid I; S2, preparing a reaction liquid II, namely mixing concentrated nitric acid and concentrated sulfuric acid to obtain the reaction liquid II; and S3, preparing 5-nitro-2-aminopyridine, namely by virtue of two pumps, respectively pumping the reaction liquid I and the reaction liquid II into a microreactor, heating to 20-60 DEG C, after the reaction is completed at atmospheric pressure, separating and purifying to obtain a yellow solid 5-nitro-2-aminopyridine. Compared with the traditional preparation method, the preparation method disclosed by the invention has the advantages of simple reaction process, short reaction time, high yield, high safety, low cost, environmental friendliness and the like.
Preparation method for malaridine intermediate 2-methoxy-5-aminopyridine
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Paragraph 0026; 0043; 0044, (2016/10/10)
The invention provides a green environment-friendly preparation method for a malaridine intermediate 2-methoxy-5-aminopyridine. The preparation method comprises the specific method: with 2-aminopyridine as a raw material, nitrating 2-aminopyridine with a mixed acid in the presence of a solvent to obtain 2-amino-5-nitropyridine; and carrying out hydrolysis, chlorination, methoxylation and reduction to obtain the intermediate 2-methoxy-5-aminopyridine. The preparation method has the advantages of simple process, short production cycle, mild reaction conditions, fewer three wastes, high product purity and yield, cheap and easily obtained raw materials, and higher economic property and environmental protection, and is suitable for industrialized production.
Microwave-assisted protection of primary amines as 2,5-dimethylpyrroles and their orthogonal deprotection
Walia, Amit,Kang, Soosung,Silverman, Richard B
, p. 10931 - 10937 (2013/11/19)
Primary amines can be readily doubly protected as N-substituted 2,5-dimethylpyrroles. Although this protecting group is stable toward strong bases and nucleophiles, long reaction times are required for both the protection and deprotection steps, generally resulting in low deprotection yields. By employing microwave irradiation, protection and deprotection reaction times are dramatically reduced. Furthermore, deprotection with dilute hydrochloric acid in ethanol increases reaction yields. Diverse deprotection conditions have been developed in conjunction with microwave irradiation, so that protection as an N-substituted 2,5-dimethylpyrrole can be orthogonal to other standard amine protecting groups, such as tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), and 9-fluorenylmethyloxycarbonyl (Fmoc).
Ligandless copper-catalyzed coupling of heteroaryl bromides with gaseous ammonia
Fantasia, Serena,Windisch, Johannes,Scalone, Michelangelo
supporting information, p. 627 - 631 (2013/04/11)
A range of different N- and S-containing heterocyclic bromides can be efficiently coupled with gaseous ammonia in the presence of copper(II) acetylacetonate [Cu(acac)2] as catalyst and in the absence of additional ligands. Unstable aminothiophenes and aminobenzothiophenes can be further reacted in situ to afford functionalized derivatives. Copyright
