2-chloro-1,4-dimethoxybenzene; 2-chloro-4-methoxyphenyl methyl ether -Drug Synthesis Database

【结构式】

【分子编号】32928

【品名】2-chloro-1,4-dimethoxybenzene; 2-chloro-4-methoxyphenyl methyl ether

【CA登记号】2100-42-7

【分子式】C₈H₉ClO₂

【分子量】172.61096

【元素组成】C 55.67% H 5.26% Cl 20.54% O 18.54%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XX)

4-Cyclohexylbutyric acid (XVIII) was converted to the corresponding acid chloride (XIX) with SOCl2. Subsequent Friedel-Crafts condensation with 2,5-dimethoxychlorobenzene (XX) yielded ketone (XXI). After bromination of (XXI) in CH2Cl2, the resulting bromoketone (XXII) was condensed with thiourea (XXIII), providing aminothiazole (XXIV). This amine was coupled with indole acid (XV) by means of BOP to give amide (XXV). The title compound was then obtained by deprotection of the tert-butyl ester with trifluoroacetic acid. In a related alternative procedure, coupling of aminothiazole (XXIV) with indole acid (XVII) gave amide (XXVI). The methyl ester was then deprotected by hydrolysis with K2CO3 in aqueous butanol.

参考文献中间体

合成目标

【1】 Brodin, R.; Boigegrain, R.; Molimard, J.-C.; Bignon, E.; Olliero, D. (Sanofi-Synthelabo ); Carboxamidothiazole derivs., preparation, pharmaceutical compsns. containing them. EP 1017693; FR 2768737; FR 2777887; WO 9915525 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	32923	1-[2-(tert-butoxy)-2-oxoethyl]-5,7-dimethyl-1H-indole-2-carboxylic acid		C₁₇H₂₁NO₄	详情	详情
(XVII)	32925	1-(2-methoxy-2-oxoethyl)-5,7-dimethyl-1H-indole-2-carboxylic acid		C₁₄H₁₅NO₄	详情	详情
(XVIII)	32926	4-cyclohexylbutyric acid	4441-63-8	C₁₀H₁₈O₂	详情	详情
(XIX)	32927	4-cyclohexylbutanoyl chloride		C₁₀H₁₇ClO	详情	详情
(XX)	32928	2-chloro-1,4-dimethoxybenzene; 2-chloro-4-methoxyphenyl methyl ether	2100-42-7	C₈H₉ClO₂	详情	详情
(XXI)	32929	1-(4-chloro-2,5-dimethoxyphenyl)-4-cyclohexyl-1-butanone		C₁₈H₂₅ClO₃	详情	详情
(XXII)	32930	2-bromo-1-(4-chloro-2,5-dimethoxyphenyl)-4-cyclohexyl-1-butanone		C₁₈H₂₄BrClO₃	详情	详情
(XXIII)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(XXIV)	32931	4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-amine; 4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-ylamine		C₁₉H₂₅ClN₂O₂S	详情	详情
(XXV)	32932	tert-butyl 2-[2-([[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]amino]carbonyl)-5,7-dimethyl-1H-indol-1-yl]acetate		C₃₆H₄₄ClN₃O₅S	详情	详情
(XXVI)	32933	methyl 2-[2-([[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]amino]carbonyl)-5,7-dimethyl-1H-indol-1-yl]acetate		C₃₃H₃₈ClN₃O₅S	详情	详情

Extended Information