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【结 构 式】

【分子编号】43806

【品名】ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate

【CA登记号】

【 分 子 式 】C14H12N2O3S

【 分 子 量 】288.32696

【元素组成】C 58.32% H 4.19% N 9.72% O 16.65% S 11.12%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XVIII)

Cyclization of 4-hydroxythiobenzamide (XIII) with 2-bromoacetoacetic acid ethyl ester (XIV) in refluxing ethanol provides 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (XV), which is formylated by reaction with hexamethylenetetramine (HMTA) and polyphosphoric acid (PPA) in hot HOAc/water to afford 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (XVI). Alkylation af (XVI) with isobutyl bromide (VI), K2CO3 and KI in DMF gives 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (XVII), which is treated with formic acid, sodium formate and hydroxylamine hydrochloride to give the already reported 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-catboxylic acid ethyl ester (IX). Finally, this compound is hydrolyzed with NaOH in THF/EtOH. Alternatively, 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (XVI) can also be treated first with formic acid, sodium formate and hydroxylamine hydrochloride to provide 2-(3-cyano-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (XVIII), which is then alkylated with isobutyl bromide (VI), K2CO3 and KI in DMF to give the already reported 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (IX).

1 Sorbera, L.A.; Castaner, J.; Rabasseda, X.; Revel, L.; TMX-67. Drugs Fut 2001, 26, 1, 32.
2 Miller, B. (American Cyanamid Co.); Thiazolylphenyl phosphates. US 3518279 .
3 Watanabe, K.; Fujii, T.; Tanaka, T.; Kondo, S. (Teijin Ltd.); Preparation method of 2-(4-alkoxy-3-cyanophenyl)thiazol derivs., and novel intermediates for the synthesis of them. JP 1994329647 .
4 Watanabe, K.; Yarino, T.; Hiramatsu, T. (Teijin Ltd.); Preparation method of 2-(4-alkoxy-3-cyanophenyl)thiazole derivs.. JP 1998045733 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 24599 1-bromo-2-methylpropane 78-77-3 C4H9Br 详情 详情
(IX) 43797 ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C18H20N2O3S 详情 详情
(XIII) 43801 4-hydroxybenzenecarbothioamide 25984-63-8 C7H7NOS 详情 详情
(XIV) 43802 ethyl 2-bromo-3-oxobutanoate C6H9BrO3 详情 详情
(XV) 43803 ethyl 2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C13H13NO3S 详情 详情
(XVI) 43804 ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C14H13NO4S 详情 详情
(XVII) 43805 ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C18H21NO4S 详情 详情
(XVIII) 43806 ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C14H12N2O3S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VI)

 

1 Zhang ZX,Xue MX, Zhao Y, et al. 2010.Synthesis of ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate. Shengyan Yaoke Daxue Xuebao, 27(5): 365~368.
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) 43804 ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C14H13NO4S 详情 详情
(I) 25109 4-hydroxybenzonitrile 767-00-0 C7H5NO 详情 详情
(II) 10180 Thiourea 62-56-6 CH4N2S 详情 详情
(III) 21337 ethyl 2-chloro-3-oxobutanoate 609-15-4 C6H9ClO3 详情 详情
(IV) 43803 ethyl 2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C13H13NO3S 详情 详情
(VI) 43806 ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C14H12N2O3S 详情 详情
(VII) 24599 1-bromo-2-methylpropane 78-77-3 C4H9Br 详情 详情
(VIII) 43797 ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate C18H20N2O3S 详情 详情
Extended Information