Emedastine difumarate, Emedastine fumarate, AL-3432A, KG-2413, LY-188695, KB-2413, Emadine(as ophthalmic formulation), Rapimine, Remicut, Daren, -Drug Synthesis Database

【结构式】

【药物名称】Emedastine difumarate, Emedastine fumarate, AL-3432A, KG-2413, LY-188695, KB-2413, Emadine(as ophthalmic formulation), Rapimine, Remicut, Daren

【化学名称】1-(2-Ethoxyethyl)-2-(4-methyl-hexahydro-1H-1,4-diazepin-1-yl)-1H-benzimidazole (E)-2-butenedioate (1:2)
　　　　　　1-(2-Ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate

【CA登记号】87233-62-3, 87233-76-9 ((2:3) salt), 87233-61-2 (free base)

【分子式】C₂₅H₃₄N₄O₉

【分子量】534.57113

【开发单位】Kanebo (Originator), Alcon (Licensee), Kowa (Licensee)

【药理作用】Allergic Skin Disorders, Treatment for, Antiallergic Ophthalmic Agents, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, Ocular Antiinflammatory and Antiinfective Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Urticaria, Treatment for, Histamine H1 Antagonists

合成路线1 合成路线2

合成路线1

A new synthesis of KB-2413 has been described: The reaction of 2-chloronitrobenzene (I) with 2-ethoxyethylamine (II) gives 1-(2-ethoxyethylamino)-2-nitrobenzene (III), which is reduced with Zn and NaOH to N-(2-ethoxyethyl-o-phenylenediamine (IV). The cyclization of (IV) with urea in amyl alcohol affords 1-(2-ethoxyethyl)benzimidazol-2-one (V), which is treated with refluxing POCl3 yielding 2-chloro-1-(2-ethoxyethyl)benzimidazole (VI). Finally, this compound is condensed with N-methylhexahydro-1,4-diazepine (VII) and treated with fumaric acid.

参考文献中间体

【1】 Awata, N.; Satomi, O.; Synthesis of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-[2-14C]benzimidazole difumarate ([14C]KB-2413). J Label Compd Radiopharm 1987, 24, 3, 331-8.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15248	1-chloro-2-nitrobenzene	88-73-3	C₆H₄ClNO₂	详情	详情
(II)	20898	2-ethoxyethylamine; 2-ethoxy-1-ethanamine	110-76-9	C₄H₁₁NO	详情	详情
(III)	20899	N-(2-ethoxyethyl)-N-(2-nitrophenyl)amine; N-(2-ethoxyethyl)-2-nitroaniline		C₁₀H₁₄N₂O₃	详情	详情
(IV)	20900	N(1)-(2-ethoxyethyl)-1,2-benzenediamine; N-(2-aminophenyl)-N-(2-ethoxyethyl)amine		C₁₀H₁₆N₂O	详情	详情
(V)	20901	1-(2-ethoxyethyl)-1,3-dihydro-2H-benzimidazol-2-one		C₁₁H₁₄N₂O₂	详情	详情
(VI)	20902	2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole; 2-(2-chloro-1H-benzimidazol-1-yl)ethyl ethyl ether		C₁₁H₁₃ClN₂O	详情	详情
(VII)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线2

The reaction of 2-chlorobenzimidazole (I) with 2-chloroethyl ethyl ether (II) by means of NaOH in DMF gives 1-(2-ethoxyethyl)benzimidazole (III), which is then condensed with N-methylhomopiperazine (IV) at 120 C.

参考文献中间体

【1】 Iemura, R.; et al. (Kanebo Pharmaceuticals, Ltd.); Benzimidazole derivatives, process for the peparation thereof and pharmaceutical composition containing the same. EP 0079545; JP 58079983 .
【2】 Serradell, M.N.; Castaner, J.; KB-2413. Drugs Fut 1985, 10, 5, 397.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	26761	2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole	4857-06-1	C₇H₅ClN₂	详情	详情
(II)	29358	1-chloro-2-ethoxyethane	628-34-2	C₄H₉ClO	详情	详情
(III)	20902	2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole; 2-(2-chloro-1H-benzimidazol-1-yl)ethyl ethyl ether		C₁₁H₁₃ClN₂O	详情	详情
(IV)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

Extended Information