IS-741
环己烷羧酰胺,N-[2-[(乙基磺酰)氨基]-5-(三氟甲基)-3-吡啶基]-,钙盐(2:1) 环己烷羧酰胺,N-[2-[(乙基磺酰)氨基]-5-(三氟甲基)-3-吡啶基]-Chemical Name: N-[2-(Ethylsulfonamido)-5-(trifluoromethyl)pyridin-3-yl]cyclohexanecarboxamide sodium salt
CAS No. 141284-73-3, 141284-77-7 (Ca salt (2:1)), 141283-87-6 (free acid), 351999-87-6 (hydrate), 141284-74-4 (monoK salt)
项目整合开发状态: Preclinical
项目研究机构: Ishihara Sangyo (Originator), Sumitomo Pharmaceuticals (Licensee)
合成路线:Nucleophilic displacement of 2-chloro-5-(trifluoromethyl)pyridine (I) with ethanesulfonamide (II) in the presence of K2CO3 in hot DMSO afforded the N-pyridyl sulfonamide (III).Subsequent nitration of (III) with fuming nitric acid in HOAc gave the 3-nitro derivative (IV).Preparation of this intermediate was also reported by displacement of 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (V) with the sodium salt of ethanesulfonamide (II).Subsequent reduction of the nitro group of (IV) to the corresponding 3-aminopyridine (VI) was carried out by means of catalytic hydrogenation,iron in HOAc,or sodium hydrosulfite as the reducing agents.Amine (VI) was coupled either with cyclohexanecarbonyl chloride (VII) or with cyclohexanecarboxylic acid (VIII) in the presence of EDC to produce the cyclohexanecarboxamide (IX).The acidic sulfonamide NH group of (IX) was finally converted to the sodium salt by treatment with NaOH.
📌 参考资料/链接：
参考文献标题:Diaminotrifluoromethylpyridine derivs.,process for their production and phospholipase A2 inhibitor containing them
文献作者:Haga,T.; Sugi,H.; Shigehara,I.; Odawara,S.; Yotsuya,S.; Kimura,H.; Yamamoto,K.(Ishihara Sangyo Kaisha,Ltd.)
参考来源:EP 0465913; JP 1993170742; JP 1994247934; JP 1994263735; US 5229403; US 5260320; US 5348967; US 5492908
📄 详细内容
合成路线:Nucleophilic displacement of 2-chloro-5-(trifluoromethyl)pyridine (I) with ethanesulfonamide (II) in the presence of K2CO3 in hot DMSO afforded the N-pyridyl sulfonamide (III).Subsequent nitration of (III) with fuming nitric acid in HOAc gave the 3-nitro derivative (IV).Preparation of this intermediate was also reported by displacement of 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (V) with the sodium salt of ethanesulfonamide (II).Subsequent reduction of the nitro group of (IV) to the corresponding 3-aminopyridine (VI) was carried out by means of catalytic hydrogenation,iron in HOAc,or sodium hydrosulfite as the reducing agents.Amine (VI) was coupled either with cyclohexanecarbonyl chloride (VII) or with cyclohexanecarboxylic acid (VIII) in the presence of EDC to produce the cyclohexanecarboxamide (IX).The acidic sulfonamide NH group of (IX) was finally converted to the sodium salt by treatment with NaOH.
参考文献标题:Synthesis and antipancreatitis activities of novel N-(2-sulfonylamino-5-trifluoromethyl-3-pyridyl)carboxamide derivatives as phospholipase A2 inhibitors
文献作者:Kimura,H.; Yotsuya,S.; Yuki,S.; Sugi,H.; Shigehara,I.; Haga,T.
参考来源:Chem Pharm Bull 1995,43(10),1696