- Preparation method of
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The invention discloses a preparing method of ponatinib. The preparing method of ponatinib comprises the steps of building a reaction system in copper salt and alkaline organic solvent with 3-halogen-parazole [1,5-a]pyrimidine being the starting point, with trimethylsilylacetylene, tetrabutylammonium fluoride and the like being raw materials in sequence and with acridine salt being a photocatalyst, and thus indirectly building a synthesizing path of ponatinib. The synthesis conditions are mild, the cost is low, and the yield of ponatinib is high.
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Paragraph 0004; 0049; 0053-0056; 0058; 0062-0065
(2020/05/01)
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- Ppm Pd-catalyzed, Cu-free Sonogashira couplings in water using commercially available catalyst precursors
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A new catalyst that derives from commercially available precursors for copper-free, Pd-catalyzed Sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Both the palladium pre-catalyst and ligand are commercially available, bench stable, and highly cost-effective. The catalyst is applicable to both aryl- and heteroaryl-bromides as educts. A wide range of functional groups are tolerated and the aqueous reaction medium can be recycled. An application to a key intermediate associated with an active pharmaceutical ingredient (ponatinib) is discussed.
- Jin, Bo,Gallou, Fabrice,Reilly, John,Lipshutz, Bruce H.
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p. 3481 - 3485
(2019/03/28)
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- PROCESSES FOR MAKING PONATINIB AND INTERMEDIATES THEREOF
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Methods are disclosed for making 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-l-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide, intermediates and pharmaceutically acceptable salts thereof.
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- A drug treating chronic granulocytic leukemia method for the preparation of
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The invention relates to a preparation method of a drug for treating chronic granulocytic leukemia, belonging to the field of medical chemistry, and specifically relates to a preparation method of 3-[2-(imidazo[1,2-b] pyridazine-3-yl) acetenyl]-4-methyl-N
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- CRYSTALLINE FORMS OF 3-(IMIDAZO[1,2-B] PYRIDAZIN-3-YLETHYNYL)-4-METHYL-N-(4-[(4-METHYLPIPERAZIN-1-YL) METHYL]-3-(TRIFLUOROMETHYL)PHENYL)BENZAMIDE AND ITS MONO HYDROCHLORIDE SALT
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Novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4- methylpiperazin-1 -yl)methyl]-3-(trifluoromethyl)phenyl}benzamide free base and 3-(imidazo[1,2- b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3
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- METHODS AND COMPOSITIONS FOR RAF KINASE MEDIATED DISEASES
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The invention discloses methods and compositions for treating or preventing RAF kinase mediated diseases or conditions by administering a compound of Formula 1: or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.
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Page/Page column 68; 69; 70
(2013/11/18)
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- Discovery of 3-[2-(imidazo[1,2- b ]pyridazin-3-yl)ethynyl]-4-methyl- N -{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant
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In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC 50s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABLT315I expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CML, including patients refractory to all currently approved therapies.
- Huang, Wei-Sheng,Metcalf, Chester A.,Sundaramoorthi, Raji,Wang, Yihan,Zou, Dong,Thomas, R. Mathew,Zhu, Xiaotian,Cai, Lisi,Wen, David,Liu, Shuangying,Romero, Jan,Qi, Jiwei,Chen, Ingrid,Banda, Geetha,Lentini, Scott P.,Das, Sasmita,Xu, Qihong,Keats, Jeff,Wang, Frank,Wardwell, Scott,Ning, Yaoyu,Snodgrass, Joseph T.,Broudy, Marc I.,Russian, Karin,Zhou, Tianjun,Commodore, Lois,Narasimhan, Narayana I.,Mohemmad, Qurish K.,Iuliucci, John,Rivera, Victor M.,Dalgarno, David C.,Sawyer, Tomi K.,Clackson, Tim,Shakespeare, William C.
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experimental part
p. 4701 - 4719
(2010/10/03)
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- BICYCLIC HETEROARYL COMPOUNDS
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This invention relates to compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.
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Page/Page column 68
(2008/06/13)
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