- High-yield synthesis method of methyl 3-aminoisonicotinate
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The invention belongs to the field of chemical pharmacy, and particularly discloses a high-yield synthesis method of methyl 3-aminoisonicotinate. According to the high-yield synthesis method, 4-picolinic acid is used as a raw material and subjected to brominating, ammonifying and esterifying to obtain methyl 3-aminoisonicotinate. The high-yield synthesis method of methyl 3-aminoisonicotinate has the advantages of mild reaction conditions, high total yield, realization of repeated use of a 3-bromo-4-picolinic acid reaction waste filtrate, improvement of the utilization rate of the raw material,reduction of resource waste, maximum reduction of the production cost of the whole process, and extremely high application value.
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Paragraph 0013; 0015; 0019; 0023
(2020/05/01)
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- Method for synthesizing 3-bromoisonicotinic acid intermediate
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The invention relates to a method for synthesizing a 3-bromoisonicotinic acid intermediate, and belongs to the technical field of pharmaceutical intermediates. The process comprises the following steps: 4-methylpyridine is adopted as a raw material, and the 4-methylpyridine is reacted with bromine under the catalysis of an aluminum trichloride catalyst to form intermediate 3-bromo-4-methylpyridine; and a novel catalyst Co0.27CuO3 is added, oxygen is introduced for oxidization to form the target product 3-bromoisonicotinic acid. According to the method provided by the invention, in the oxidation reaction process, water is used as a solvent, the novel catalyst Co0.27CuO3 is introduced, the oxygen is used as an oxidant to replace a traditional KMnO4 oxidant, so that pollution of heavy metalsto the environment can be avoided; because the novel catalyst is not affected by the reaction environment, catalytic activity of the novel catalyst is not reduced, and after 25 cycles, activity of thecatalyst is not significantly reduced; and the method has the advantages of greatly improving the yield, reducing the costs, improving the safety, saving the energy, and the like, and conforms to modern chemical industry production requirements of a green reaction.
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Paragraph 0010
(2019/07/04)
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- Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
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Abstract The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl)ate their target proteins using NAD+ as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with β-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused >1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2.
- Kumpan, Katerina,Nathubhai, Amit,Zhang, Chenlu,Wood, Pauline J.,Lloyd, Matthew D.,Thompson, Andrew S.,Haikarainen, Teemu,Lehti?, Lari,Threadgill, Michael D.
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supporting information
p. 3013 - 3032
(2015/08/03)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
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The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a pyrethroid compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a pyrethroid compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 210-211
(2011/05/06)
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- HARMFUL ARTHROPOD CONTROL COMPOSITION, AND FUSED HETEROCYCLIC COMPOUND
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Disclosed is a harmful arthropod control composition comprising, as an active ingredient, a fused heterocyclic compound represented by formula (1) [wherein A1 and A2 independently represent a nitrogen atom or the like; R1 and R4 independently represent a halogen atom or the like; R2 and R3 independently represent a halogen atom or the like; R5 and R6 independently represent a linear C1-C6 hydrocarbon group which may be substituted, or the like (provided that both R5 and R6 cannot represent a hydrogen atom simultaneously); and n represents 0 or 1]. The harmful arthropod control composition has an excellent efficacy to control harmful arthropods.
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Page/Page column 126
(2011/02/18)
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- HARMFUL ARTHROPOD CONTROL COMPOSITION, AND FUSED HETEROCYCLIC COMPOUND
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Disclosed is a harmful arthropod control composition comprising, as an active ingredient, a fused heterocyclic compound represented by formula (1) [wherein A1 and A2 independently represent a nitrogen atom or the like; R1 and R4 independently represent a halogen atom or the like; R2 and R3 independently represent a halogen atom or the like; R5 and R6 independently represent a linear C1-C6 hydrocarbon group which may be substituted, or the like (provided that both R5 and R6 cannot represent a hydrogen atom simultaneously); and n represents 0 or 1]. The harmful arthropod control composition has an excellent efficacy to control harmful arthropods.
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Page/Page column 79
(2011/04/13)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
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The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a neonicotinoid compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a neonicotinoid compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 210
(2011/04/25)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
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The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and pyriproxyfen; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and pyriproxyfen to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 209
(2011/05/06)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
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The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and pyridalyl; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and pyridalyl to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 209
(2011/05/06)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
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The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a diamide compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a diamide compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 213-214
(2011/05/06)
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- Novel 3beta-amino azabicyclooctane heteroaromatic amid derivatives preparation method and therapeutic uses thereof
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The invention concerns compounds of general formula 1, wherein: A, B, D and E represent one or two nitrogen atoms, the others being carbon atoms; X represents a S or, a O, thereby forming a bicyclic fused heteroaromatic, such as thieno[2,3-b]pyridine, furo[2,3-b]pyridine, thieno[3,2-b]pyridine, furo[3,2-b]pyridine, thieno[2,3-b]pyrazine, furo[2,3-b]pyrazine, thieno[2,3-c]pyridine, furo[2,3-c]pyridine, thieno[3,2-c]pyridine and furo[3,2-c]pyridine; R1 represents a linear or branched C1-C6 alkoxy group, a linear or branched C1-C6 alkylthio group; R2 represents a linear, branched, cyclic C2-C8 group, a 2- or 3- thienylmethyl group, or a benzyl group optionally substituted by one or several halogens, F, Cl, Br, I, C1-C4 alkyl, C1-C4 alkoxy, CF3, CN, NO2, OH; and their pharmaceutically acceptable salts. Said compounds are anti-dopaminergic agents.
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Page/Page column 12
(2010/02/11)
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- Application of organolithium compounds in organic synthesis. Part 19. Synthetic strategies based on aromatic metallation. A concise regiospecific synthesis of 3-halogenated picolinic and isonicotinic acids
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The synthesis of the halogenated picolin- and isonicotinalides (3) and (4) via metallation (n-BuLi) of the anilides (1) and (2) and then the reaction of the generated bis-lithiated anilides with halogenating agents (CCl3-CCl3, CH2Br-CH2Br, I2) followed by subsequent acidic hydrolysis of (3) and (4), as a way of regiospecific transformation of picoline and isonicotine acids into their C3-halogenated derivatives, is described.
- Epsztajn,Plotka,Grabowska
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p. 1075 - 1086
(2007/10/03)
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- Herbicidal 1-pyridyltetrazolinones
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Herbicidal tetrazolinone derivatives of the formula: STR1 in which R1 is alkyl, haloalkyl, cycloalkyl, alkenyl, haloalkenyl, alkynyl or phenyl, and R2 is alkyl, haloalkyl, cycloalkyl, alkenyl, haloalkenyl, alkynyl or phenyl, or R1 and R2 together with the nitrogen atom to which they are bonded form an optionally benzofused heterocyclic ring, which is optionally substituted by C1-4 alkyl, n is 0, 1, 2 or 3, and R3 each independently is nitro, halogen, alkyl, haloalkyl, alkylthio or phenoxy.
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- 2-(aza-9-fluorenonyl)carbapenem antibacterial agents
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Carbapenems of the formula STR1 wherein a suitably substituted aza-9-fluorenone is attached at the 2-position of the carbapenem are useful antibacterial agents.
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