- (PYRIDIN-2-YL)AMINE DERIVATIVES AS TGF-BETA R1 (ALK5) INHIBITORS FOR THE TREATMENT OF CANCER
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The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder associated with ΤGFβR1 activity, such as a cancer or fibrosis. The invention provides compounds of Formula (I) and Formula (II) as further described herein having an acidic moiety that enhances tissue specificity for targeted tissues and organs. The invention includes pharmaceutical compositions, pharmaceutical combinations, and methods of use of these compounds for treating conditions including cancer or fibrosis.
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Paragraph 00266
(2020/07/15)
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- Synthesis method of 2, 5-dimethyl-3-bromopyridine
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The invention relates to the field of organic chemistry, in particular to a synthesis method of 2, 5-dimethyl-3-bromopyridine. The synthesis method comprises the following steps: 1, reacting diethyl malonate with an alkali metal to generate a salt, dropwisely adding a toluene solution of 2 methyl-3-nitro-5-chloropyridine to perform condensation reaction, and decarboxylating under acidic conditionsto obtain 2, 5-dimethyl-3-nitropyridine; 2, carrying out hydrogenation reduction, suction filtration and filtrate concentration on the obtained 2, 5-dimethyl-3-nitropyridine by taking methanol as a solvent under the catalysis of Pd/C so as to obtain 2, 5-dimethyl-3-aminopyridine;, and 3, reacting the obtained 2, 5-dimethyl-3-aminopyridine with an acid to generate a salt, cooling to -9 DEG C to 4DEG C, dropwise adding liquid bromine, dropwise adding a sodium nitrite aqueous solution after dropwise adding of liquid bromine, adjusting the pH value of an obtained solution to be higher than 7 after dropwise adding of the sodium nitrite aqueous solution, and then extracting, drying and concentrating to obtain 2, 5-dimethyl-3-bromopyridine. The method provided by the invention has the beneficial effects of mild reaction conditions, high yield, easily available raw materials, low cost, short process route and an industrial prospect.
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Paragraph 0023-0024; 0027-0028; 0031-0032
(2020/03/09)
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- A 2, 5 - dimethyl -3 - bromo pyridine synthesis method
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The invention relates to the field of organic chemistry, in particular to a 2, 5 - dimethyl - 3 - bromo pyridine synthesis method, comprises the following steps: 1, malonic acid diethyl ester and alkali metal reaction to produce salt, then dropwise 2 methyl - 3 - nitro - 5 chloro pyridine to a toluene solution of a condensation reaction, after decarboxylation under acidic conditions shall be 2, 5 - dimethyl - 3 - nitro pyridine; 2, 2, 5 - dimethyl - 3 - nitro pyridine in under the catalysis of the Pd/C, methanol as the solvent, hydrogen reduction, filtered, the filtrate is concentrated, shall be 2, 5 - dimethyl - 3 - aminopyridine; 3, 2, 5 - dimethyl - 3 - aminopyridine first with an acid generating salt, cooling to - 9 °C - 4 °C, [...], drops the instillment sodium nitrite aqueous solution, pH adjusting solution is dropped is alkaline, and then extracted, drying, concentration, shall be 2, 5 - dimethyl - 3 - bromo pyridine. The method of the invention is beneficial effect: mild reaction conditions, high yield, and raw materials are easy, and the cost is low, the process route is short, and has industrial prospects.
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Paragraph 0020; 0023; 0024; 0027; 0028; 0031; 0032
(2019/05/28)
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- A 2, 5 - dimethyl - 3 - bromo pyridine synthesis method (by machine translation)
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The invention relates to the field of organic chemistry, in particular to a 2, 5 - dimethyl - 3 - bromo pyridine synthesis method, comprises the following steps: 1, malonic acid diethyl ester and alkali metal reaction to produce salt, then dropwise 2 methyl - 3 - nitro - 5 chloro pyridine to a toluene solution of a condensation reaction, after decarboxylation under acidic conditions shall be 2, 5 - dimethyl - 3 - nitro pyridine; 2, 2, 5 - dimethyl - 3 - nitro pyridine in under the catalysis of the Pd/C, methanol as the solvent, hydrogen reduction, filtered, the filtrate is concentrated, shall be 2, 5 - dimethyl - 3 - aminopyridine; 3, 2, 5 - dimethyl - 3 - aminopyridine first with an acid generating salt, cooling to - 9 °C - 4 °C, instillment fluid bromine, drops the instillment sodium nitrite aqueous solution, pH adjusting solution is dropped is alkaline, and then extracted, drying, concentration, shall be 2, 5 - dimethyl - 3 - bromo pyridine. The method of the invention is beneficial effect: mild reaction conditions, high yield, and raw materials are easy, and the cost is low, the process route is short, and has industrial prospects. (by machine translation)
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Paragraph 0023; 0024; 0028; 0032
(2017/09/26)
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- PYRIDYLAMIDINE COMPOUND OR SALT THEREOF, AND AGRICULTURAL OR HORTICULTURAL FUNGICIDE COMPOSITION CONTAINING THE SAME AS ACTIVE INGREDIENT
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An agricultural or horticultural fungicide composition having stabilized high plant disease control effect is provided. The agricultural or horticultural fungicide composition contains a pyridylamidine compound represented by the formula (I): or a salt th
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Page/Page column 17
(2009/09/04)
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- Nitration of Aromatic and Heteroaromatic Compounds by Dinitrogen Pentaoxide
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Nitration of benzene and monosubstituted benzenes in liquid SO2 by dinitrogen pentaoxide at - 11 deg C gave the corresponding nitroarenes with substitution patterns similar to those obtained by nitrations with HNO3-H2SO4.For acetophenone an o/m ratio of 0.94 was obtained.The yields were dependent on the substituents.With a 1:1 ratio of arene: N2O5 the yields varied from 73percent for toluene to 0.4percent for nitrobenzene as substrates.From competition experiments and the nitration of bibenzyl it was concluded that the reaction was faster than the macroscopic rate of mixing.The qualitative order of reactivity for PhX was X = OCH3>CH3>H>Cl>CH3CO>NO2.Nitration with N2O5 in liquid CO2 gave similar results.Nitration of pyrimidine, pyrrole, imidazole and indole with N2O5-SO2 gave no nitrated products.With thiophene, 2- (34percent) and 3-nitrothiophene (5percent) together with 2,4-(16percent) and 2,5-dinitrothiophene (8percent) were obtained.With pyridine, mono- and di-methylpyridines, quinoline, isoquinoline and 4-phenylpyridine nitration of the pyridine ring was obtained.The yields varied from ca. 70percent to 16percent, except for 3,5-, 2,5- and 2,6-dimethylpyridine for which only traces of nitro-dimethylpyridines were obtained.The reaction with the pyridines appears to be intramolecular both in the SO2 phase and in the water phase used for quenching the reaction.The reaction was proposed to proceed by a complex formed in liquid SO2:
- Bakke, Jan M.,Hegbom, Ingrid,Oevreeide, Elin,Aaby, Kjersti
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p. 1001 - 1006
(2007/10/02)
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