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【结 构 式】

【药物名称】

【化学名称】1(R)-[3-(Cyclopentyloxy)-4-methoxyphenyl]-3(S)-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanecarbonitrile

【CA登记号】162101-90-8 (cis-isomer)

【 分 子 式 】C22H27N3O3

【 分 子 量 】381.47879

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Asthma Therapy, Bronchodilators, RESPIRATORY DRUGS, Phosphodiesterase IV Inhibitors

合成路线1

The reaction of 5-cyano-5-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxocyclohexanecarboxylic acid methyl ester (I) with trifluoromethanesulfonic anhydride gives the enol triflate (II), which is desulfonated with triphenylphosphine, palladium acetate and formic acid yielding 5-cyano-5-(3-cyclopentyloxy-4-methoxyphenyl)-1-clohexene-1-carboxylic acid methyl ester (III). The hydrogenation of the double bond of (III) with H2 over Pd/C in methanol affords the cis carboxylic ester (IV), which is hydrolyzed with KOH in in methanol to provide the free carboxylic acid (V). The reaction of (V) with isobutyl chloroformate and then with NH4OH gives the corresponding amide (VI), which is finally cyclized with N,N-dimethylacetamide dimethylacetal (VII) by heating at 110 C to obtain target compound as a racemate.

1 Board, M.; Newsholme, E.A. (Isis Pharmaceuticals, Inc.); Use of glucokinase inhibitors for the manufacture of a medicament for treating tumours. WO 9503809 .
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) 16515 methyl 5-cyano-5-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxocyclohexanecarboxylate C21H25NO5 详情 详情
(II) 26690 methyl 5-cyano-5-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-[[(trifluoromethyl)sulfonyl]oxy]-1-cyclohexene-1-carboxylate C22H24F3NO7S 详情 详情
(III) 26691 methyl 5-cyano-5-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-cyclohexene-1-carboxylate C21H25NO4 详情 详情
(IV) 26692 methyl (1S,3R)-3-cyano-3-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylate C21H27NO4 详情 详情
(V) 26693 (1S,3R)-3-cyano-3-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid C20H25NO4 详情 详情
(VI) 26694 (1S,3R)-3-cyano-3-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxamide C20H26N2O3 详情 详情
(VII) 22915 1,1-dimethoxy-N,N-dimethyl-1-ethanamine;N,N-dimethylacetamide dimethylacetal; N-(1,1-dimethoxyethyl)-N,N-dimethylamine 18871-66-4 C6H15NO2 详情 详情
Extended Information