- Preparation method of 3-methylquinoline-8-sulfonyl chloride
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The invention belongs to the field of fine chemical product production, and particularly relates to a preparation method of 3-methylquinoline-8-sulfonyl chloride, and the method comprises the following steps: (1) carrying out catalytic cyclization on 2-aminobenzene sulfonic acid serving as an initial raw material, propionaldehyde and paraformaldehyde in a deep eutectic solvent to obtain 3-methylquinoline-8-sulfonic acid; and (2) carrying out acylating chlorination on the generated 3-methylquinoline-8-sulfonic acid under the action of an organic alkali by using bis (trichloromethyl) carbonate as a chlorinating agent, thereby obtaining the 3-methylquinoline-8-sulfonyl chloride. The method has the advantages of simple operation process, easily available raw material, low cost, no generation of harmful gases in the whole process, meeting of safety and environmental protection requirements, and facilitation of large-scale production.
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Paragraph 0046-0049; 0058-0077
(2020/03/17)
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- SSR182289A, a selective and potent orally active thrombin inhibitor
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SSR182289A 1 is the result of a rational optimisation process leading to an orally active thrombin inhibitor. The structure incorporates an original 2-(acetylamino)-[1,1′-biphenyl]-3-sulfonyl N-terminal motif, a central L-Arg surrogate carrying a weakly basic 3-amino-pyridine, and an unusual 4-difluoropiperidine at the C-terminus. Its synthesis is convergent and palladium catalysis has been employed for the construction of the key C-C bonds: Suzuki coupling for the bis-aryl fragment and Sonogashira reaction for the δ-ε bond of the central amino-acid chain. The compound is a potent inhibitor of thrombin's activities in vitro and demonstrates potent oral anti-thrombotic potencies in three rat models of thrombosis. The observed in vitro potency could be rationalized through the examination of the interactions within the SSR182289A 1 - thrombin crystal structure. SSR182289A 1, has been therefore selected for further development.
- Altenburger, Jean-Michel,Lassalle, Gilbert Y.,Matrougui, Mostapha,Galtier, Daniel,Jetha, Jean-Claude,Bocskei, Zsolt,Berry, Christopher N.,Lunven, Catherine,Lorrain, Janine,Herault, Jean-Pascal,Schaeffer, Paul,O'Connor, Stephen E.,Herbert, Jean-Marc
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p. 1713 - 1730
(2007/10/03)
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