- Synthetic method of erlotinib intermediate
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The invention relates to a synthesis method of an erlotinib intermediate, which comprises the following steps: reacting 2-bromo-4,5-dimethoxybenzonitrile with formamidine hydrochloride under the actions of alkali and a catalyst to generate a compound 3; reacting with 1-bromo-triethynylbenzene under the catalysis of alkali to generate a compound 2; carrying out a reaction on the compound 2 with 48%hydrobromic acid under the action of a catalyst to obtain a compound 1. The method is mild in condition, simple in step, safe, environmentally friendly and suitable for industrial production.
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Paragraph 0018; 0029-0038; 0047-0048
(2020/05/29)
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- Discovery and optimization of 1-(4-chloro-3-(trifluoromethyl)-phenyl)-3-(2-(amino)pyridin-3-yl)ureas as novel kdr kinase inhibitors
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Kinase insert Domain-containing Receptor (KDR) is one of the currently validated targets for anticancer drug discovery and development. Herein, a series of o-amino-arylurea derivatives have been synthesized and evaluated for their kinase inhibitory activity. The optimization on the basis of biological screening and molecular modeling resulted in obvious increase in KDR kinase inhibitory activity compared with the hit compound. Eventually, we identified a potent inhibitor 5a of 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-((quinolin-4-ylmethyl) amino)pyridin-3-yl)urea scaffold against KDR (IC50 = 0.0689 μM), which can serve as good starting point for further KDR inhibitor optimization and development.
- Jiao, Yu,Huang, Fei,Xu, Pengfei,Zhang, Yanmin,Yang, Shangyan,Zhang, Danfeng,Lu, Tao,Tang, Weifang
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p. 328 - 337
(2016/07/06)
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- Discovery and Optimization of 1-(4-chloro-3-(trifluoromethyl)-phenyl)-3-(2-(amino)pyridin-3-yl)ureas as Novel KDR Kinase Inhibitors
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Kinase insert Domain-containing Receptor (KDR) is one of the currently validated targets for anticancer drug discovery and development. Herein, a series of o-amino-arylurea derivatives have been synthesized and evaluated for their kinase inhibitory activity. The optimization on the basis of biological screening and molecular modeling resulted in obvious increase in KDR kinase inhibitory activity compared with the hit compound. Eventually, we identified a potent inhibitor 5a of 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-((quinolin-4-ylmethyl) amino)pyridin-3-yl)urea scaffold against KDR (IC50 = 0.0689 μM), which can serve as good starting point for further KDR inhibitor optimization and development.
- Jiao, Yu,Huang, Fei,Xu, Pengfei,Zhang, Yanmin,Yang, Shangyan,Zhang, Danfeng,Lu, Tao,Tang, Weifang
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p. 328 - 337
(2016/10/12)
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- Mild and highly selective palladium-catalyzed monoarylation of ammonia enabled by the use of bulky biarylphosphine ligands and palladacycle precatalysts
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A method for the Pd-catalyzed arylation of ammonia with a wide range of aryl and heteroaryl halides, including challenging five-membered heterocyclic substrates, is described. Excellent selectivity for monoarylation of ammonia to primary arylamines was achieved under mild conditions or at rt by the use of bulky biarylphosphine ligands (L6, L7, and L4) as well as their corresponding aminobiphenyl palladacycle precatalysts (3a, 3b, and 3c). As this process requires neither the use of a glovebox nor high pressures of ammonia, it should be widely applicable.
- Cheung, Chi Wai,Surry, David S.,Buchwald, Stephen L.
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supporting information
p. 3734 - 3737
(2013/08/23)
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- Polycyclic N-heterocyclic compounds, part 67: Reaction of 6,7-substituted N-(quinazolin-4-yl)amidine derivatives with hydroxylamine hydrochloride: Formation of in vitro inhibitors of pentosidine
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Reactions of N-(quinazolin-4-yl)amidines and their amide oximes with hydroxylamine hydrochloride gave cyclization products that were formed by an initial ring cleavage of the pyrimidine component followed by a ring closure formation of 1,2,4-oxadiazole to
- Okuda, Kensuke,Muroyama, Hideki,Hirota, Takashi
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experimental part
p. 1407 - 1413
(2012/01/05)
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- Microwave-assisted thermal decomposition of formamide: A tool for coupling a pyrimidine ring with an aromatic partner
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Rapid and efficient generation of CO and NH3 in the reaction mixture via microwave-assisted thermal decomposition of formamide may represent a significant improvement over existing methods for coupling a pyrimidine ring with an aromatic partner. This work aims at alerting readers on the probability to observe interesting phenomena and reactions when this very powerful heating mode is associated with thermally unstable reagents.
- Loidreau, Yvonnick,Besson, Thierry
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experimental part
p. 4852 - 4857
(2011/08/06)
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