2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole -Drug Synthesis Database

【结构式】

【分子编号】26761

【品名】2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole

【CA登记号】4857-06-1

【分子式】C₇H₅ClN₂

【分子量】152.58288

【元素组成】C 55.1% H 3.3% Cl 23.24% N 18.36%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(I)

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

合成目标

【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

合成路线2

该中间体在本合成路线中的序号：(I)

N-Alkylation of 2-chlorobenzimidazole (I) with benzyl bromide (II) by means of NaH in DMF provides benzylated derivative (III), which is converted into the desired compound by heating with piperazine (IV).

参考文献中间体

合成目标

【1】 Parihar, H.S.; et al.; 5-HT3R binding of lerisetron: An interdisciplinary approach to drug-receptor interactions. Bioorg Med Chem Lett 2001, 11, 16, 2133.
【2】 Orjales, A.; et al.; New 2-piperazinylbenzimidazole derivatives as 5-HT3 antagonists. Synthesis and pharmacological evaluation. J Med Chem 1997, 40, 4, 586.
【3】 Orjales-Venero, A.; Garcia-Dominguez, N.; Rubio-Royo, V.; Rodes-Solanes, R. (FAES); New 2-piperazinylbenzimidazole derivs.. EP 0512939; JP 1995002795; US 5256665 .

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)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(III)	49687	1-Benzyl-2-chloro-1H-benzoimidazole		C₁₄H₁₁ClN₂	详情	详情
(IV)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The reaction of 2-chlorobenzimidazole (I) with N,N'-dimethylprolylene-1,3-diamine (II) by heating at 130 C gives N-(1H-benzimidazol-2-yl)-N,N'-dimethylpropylene-1,3-diamine (III), which is treated with tert-butoxycarbonyl anhydride yielding the carbamate (IV). The condensation of (IV) with 4-fluorobenzyl chloride (V) by means of K2CO3 in DMF affords N-(benzyloxycarbonyl)-N'-[1-(4-fluorobenzyl)benzimidazol-2-yl)-N,N'-dimethylpropylene-1,3-diamine (VI), which is deprotected with trifluoroacetic acid providing the secondary amine (VII). Finally, this compound is condensed with phenyl N-[3,5-bis(trifluoromethyl)benzyl]carbamate (VIII) by heating at 120 C.

参考文献中间体

合成目标

【1】 Kamikawaji, Y.; Tanikawa, K.; Yamamoto, A.; Hirotsuka, M.; Iwama, T.; Fujita, Y. (Nissan Chemical Industry, Ltd.); Benzimidazole deriv.. EP 0980359; JP 1999315071; US 6114369; WO 9850368 .

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)	26762	N-methyl-N-[3-(methylamino)propyl]amine	111-33-1	C₅H₁₄N₂	详情	详情
(III)	26763	N(1)-(1H-benzimidazol-2-yl)-N(1),N(3)-dimethyl-1,3-propanediamine		C₁₂H₁₈N₄	详情	详情
(IV)	26764	tert-butyl 3-[1H-benzimidazol-2-yl(methyl)amino]propyl(methyl)carbamate		C₁₇H₂₆N₄O₂	详情	详情
(V)	12354	4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene	352-11-4	C₇H₆ClF	详情	详情
(VI)	26765	tert-butyl 3-[[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl](methyl)amino]propyl(methyl)carbamate		C₂₄H₃₁FN₄O₂	详情	详情
(VII)	26766	N-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-N-methyl-N-[3-(methylamino)propyl]amine		C₁₉H₂₃FN₄	详情	详情
(VIII)	26767	phenyl 3,5-bis(trifluoromethyl)benzylcarbamate		C₁₆H₁₁F₆NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

2-Chlorobenzimidazole (I) was treated with NaH in DMF and the resulting sodium salt was alkylated with 4-[2-(2-chloroethoxy)ethoxy]-2,3,6-trimethylphenol (II) to give (III). Subsequent displacement of the chlorine of (III) with N-methyl homopiperazine (IV) at 130 C produced the desired 2-(homopiperazino)benzimidazole, which was finally treated with fumaric acid in EtOH to yield the corresponding bis fumarate salt.

参考文献中间体

合成目标

【1】 Nakano, H.; Inoue, T.; Inagaki, N.; Taguchi, T.; Satoh, T.; Kawasaki, N.; Nagai, H.; Matsumoto, H.; Miyataka, H.; Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action. Bioorg Med Chem 2000, 8, 2, 373.
【2】 Nakano, H.; Inoue, T.; Inagaki, N.; Taguchi, T.; Matsumoto, H.; Satoh, T.; Miyataka, H.; Kawasaki, N.; Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action. Chem Pharm Bull 1999, 47, 11, 1573.

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)	38944	4-[2-(2-chloroethoxy)ethoxy]-2,3,6-trimethylphenol		C₁₃H₁₉ClO₃	详情	详情
(III)	38945	4-[2-[2-(2-chloro-1H-benzimidazol-1-yl)ethoxy]ethoxy]-2,3,6-trimethylphenol		C₂₀H₂₃ClN₂O₃	详情	详情
(IV)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(VI)

Alkylation of 2-chlorobenzimidazole (VI) with iodomethane and NaOH leads to 2-chloro-1-methylbenzimidazole (VII). The 2-chloro group of (VII) is then displaced with hydrazine hydrate to afford hydrazine (VIII). Finally, condensation between ketone (V) and hydrazine (VIII) gives rise to the target hydrazone.

参考文献中间体

合成目标

【1】 Easmon, J.; Fürtinger, S.; Lackner, G. ; Magreiter, E.; Hofmann, J.; Heinisch, G.; Puerstinger, G.; Hydrazones derived from monosubstitued 2-acetylpyridines and 2-hydrazino-1-methylbenzimidazole: Synthesis and biological studies. Eur J Cancer 2002, 38, Suppl. 7.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	62795	1-(5-methyl-2-pyridinyl)-1-ethanone		C₈H₉NO	详情	详情
(VI)	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
(VII)	62796	2-chloro-1-methyl-1H-benzimidazole		C₈H₇ClN₂	详情	详情
(VIII)	62797	2-hydrazino-1-methyl-1H-benzimidazole		C₈H₁₀N₄	详情	详情

Extended Information