2-(chloromethyl)-4,5-dihydro-1H-imidazole -Drug Synthesis Database

【结构式】

【分子编号】17330

【品名】2-(chloromethyl)-4,5-dihydro-1H-imidazole

【CA登记号】

【分子式】C₄H₇ClN₂

【分子量】118.56576

【元素组成】C 40.52% H 5.95% Cl 29.9% N 23.63%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(V)

2) By reaction of 4-methoxybenzylamine (I) with diethyl iminocarbonate (A) in water to give diethyl N-(4-methoxybenzyl)iminocarbonate (II), followed by treatment with methylamine in water - ethanol - H2SO4.

参考文献中间体

合成目标

【1】 Najer, H.; Giudidelli, J.F. (Sanofi-Synthelabo); 2-(2'-Cyclopropylphenoxymethyl)-2-imidazoline and pharmaceutically acceptable salts thereof. DE 2234714; ES 404927; FR 2145423; GB 1386355; US 3803130 .
【2】 Hillier, K.; Castaner, J.; Cirazoline. Drugs Fut 1978, 3, 5, 359.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(I)	39809	2-cyclopropylphenol	10292-60-1	C₉H₁₀O	详情	详情
(II)	14443	2-chloroacetonitrile; chloroacetonitrile	107-14-2	C₂H₂ClN	详情	详情
(III)	39810	2-(2-cyclopropylphenoxy)acetonitrile		C₁₁H₁₁NO	详情	详情
(IV)	39811	ethyl 2-(2-cyclopropylphenoxy)ethanimidoate		C₁₃H₁₇NO₂	详情	详情
(V)	17330	2-(chloromethyl)-4,5-dihydro-1H-imidazole		C₄H₇ClN₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of N-(3-hydroxyphenyl)-N-(4-methylphenyl)amine (I) with 2-(chloromethyl)-4,5-dihydro-1H-imidazole (II) by heating at 150-60 C without solvent or in o-dichlorobenzene gives phentolamine as hydrochloride salt (III), which is treated with ammonia to obtain the free base, and finally salified with methanesulfonic acid in ethanol.

参考文献中间体

合成目标

【1】 Miescher, K.; Marxer, A.; Urech, E.; 2-Aminoalkyl-imidazoline. Helv Chim Acta 1950, 33, 5, 1386-407.
【2】 Miescher, K.; Marxer, A.; Urech, E. (Novartis Corp.); 2-(N,N-Diphenyl-aminomethyl)imidazoles. US 2503059 .

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)	17329	3-(4-toluidino)phenol	61537-49-3	C₁₃H₁₃NO	详情	详情
(II)	17330	2-(chloromethyl)-4,5-dihydro-1H-imidazole		C₄H₇ClN₂	详情	详情
(III)	17331	3-[(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-methylanilino]phenol hydrochloride		C₁₇H₁₉N₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

2-(Methylthio)aniline (I) was alkylated with 2-(chloromethyl)-2-imidazoline hydrochloride (II) in phenol at 120 C to afford the condensation product (III). Subsequent oxidation of the thioether functionality of (III) with m-chloroperbenzoic acid gave rise to the target sulfone.

参考文献中间体

合成目标

【1】 Hodson, S.J.; Navas, F. III; Bishop, M.J.; Bigham, E.C.; Garrison, D.T.; Drewry, D.H.; Speake, J.D. (Glaxo Group Ltd.); Imidazoline derivs. as alpha-1A adrenoceptor ligands. WO 0066563 .

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)	49148	2-(Methylthio)aniline; o-Aminothioanisole; o-Thioanisidine; 2-Aminothioanisole; 2-Methylmercaptoaniline; o-(methylthio)aniline	2987-53-3	C₇H₉NS	详情	详情
(II)	17330	2-(chloromethyl)-4,5-dihydro-1H-imidazole		C₄H₇ClN₂	详情	详情
(III)	49149	N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-N-[2-(methylsulfanyl)phenyl]amine; N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2-(methylsulfanyl)aniline		C₁₁H₁₅N₃S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

5-Methoxy-2-methylbenzothiazole (I) is hydrolyzed by NaOH in ethylene glycol to furnish 2-amino-4-methoxythiophenol (II), which is further alkylated with iodomethane and potassium tert-butoxide, yielding thioether (III). Condensation of aniline (III) with 2-(chloromethyl)imidazoline (IV) in the presence of phenol provides (V). After oxidation of sulfide (V) to the corresponding sulfone by means of m-chloroperbenzoic acid, the title compound is isolated as its fumarate salt (1,2).

参考文献中间体

合成目标

【1】 Hodson, S.J.; Bishop, M.J.; Speake, J.D.; Navas, F. III; Garrison, D.T.; Bigham, E.C.; Saussy, D.L. Jr.; Liacos, J.A.; Irving, P. E.; Gobel, M.J.; Sherman, B.W.; 2-(Anilinomethyl)imidazolines as alpha1 adrenergic receptor agonists: The discovery of alpha1a subtype selective 2'-alkylsulfonyl-substituted analogues. J Med Chem 2002, 45, 11, 2229.
【2】 Hodson, S.J.; Navas, F. III; Bishop, M.J.; Bigham, E.C.; Garrison, D.T.; Drewry, D.H.; Speake, J.D. (Glaxo Group Ltd.); Imidazoline derivs. as alpha-1A adrenoceptor ligands. WO 0066563 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63668	5-methoxy-2-methyl-1,3-benzothiazole; methyl 2-methyl-1,3-benzothiazol-5-yl ether	C₉H₉NOS	详情	详情
(II)	63669	2-amino-4-methoxybenzenethiol; 2-amino-4-methoxyphenylhydrosulfide	C₇H₉NOS	详情	详情
(III)	63670	5-methoxy-2-(methylsulfanyl)aniline; 5-methoxy-2-(methylsulfanyl)phenylamine	C₈H₁₁NOS	详情	详情
(IV)	17330	2-(chloromethyl)-4,5-dihydro-1H-imidazole	C₄H₇ClN₂	详情	详情
(V)	63671	N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-5-methoxy-2-(methylsulfanyl)aniline; N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-N-[5-methoxy-2-(methylsulfanyl)phenyl]amine	C₁₂H₁₇N₃OS	详情	详情

Extended Information