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【结 构 式】

【分子编号】32143

【品名】N-methyl-N-phenylacetamide

【CA登记号】579-10-2

【 分 子 式 】C9H11NO

【 分 子 量 】149.19248

【元素组成】C 72.46% H 7.43% N 9.39% O 10.72%

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:(V)

GW150526 was easily prepared starting from the known 3-unsubstituted indole derivative (IV) following the general synthetic route described in Scheme 20235901a. The known indole derivative (IV) was formylated at the C-3 position according to the well known Vilsmaier-Haack procedure obtaining the intermediate (VI) in high yield. The subsequent Wittig-type olefination reaction afforded the compound (VII) with high regio control in the formation of the olefinic moiety. The hydrolysis of the ethyl ester group afforded GV-150526 as sodium salt derivative.

1 Di Fabio, R.; Cugola, A.; Donati, D.; Ferinai, A.; Gaviraghi, G.; Ratti, E.; Trist, D.G.; Reggiani, A.; Identification and pharmacological characterization of GV150526, a novel glycine antagonist as potent neuroprotective agent. Drugs Fut 1998, 23, 1, 61.
2 Salituro, F.G.; et al.; 3-(2-Carboxyindol-3-yl)propionic acid derivatives: Antagonists of the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspartate receptor complex. J Med Chem 1990, 33, 11, 2946-8.
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) 28066 1-(3,5-dichlorophenyl)hydrazine 39943-56-1 C6H6Cl2N2 详情 详情
(II) 17491 ethyl acetate 141-78-6 C4H8O2 详情 详情
(III) 32141 ethyl 2-[(E)-2-(3,5-dichlorophenyl)hydrazono]propanoate C11H12Cl2N2O2 详情 详情
(IV) 32142 ethyl 4,6-dichloro-1H-indole-2-carboxylate C11H9Cl2NO2 详情 详情
(V) 32143 N-methyl-N-phenylacetamide 579-10-2 C9H11NO 详情 详情
(VI) 32144 ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate C12H9Cl2NO3 详情 详情
(VII) 32145 N-phenyl-2-(triphenylphosphoranylidene)acetamide C26H22NOP 详情 详情
(VIII) 32147 ethyl 3-[(E)-3-anilino-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate C20H16Cl2N2O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

Alternatively, for the synthesis of analogues of GV-150526 substituted at the terminal phenyl ring belonging to the C-3 side chain as shown in Scheme 20235902a, compound (I) was transformed int the intermediate (III) in high yield. Following chemoselective deprotection of the tert-butyl ester group, the free carboxylic acid derivative (IV) was submitted to amidation reaction using different synthetic methods. In particular, the activation of the carboxy group through the formation of the corresponding 2-pyridyl thioester, generated in situ by the mild oxidation-reduction condensation reaction in the presence of 2,2'-dipyridyl disulfide and PPh3, was found to be highly efficient, also in the case of poor nucleophilic aromatic amines, affording the desired amide derivatives (VI) in high yield (either from the isolated 2-pyridyl thioester intermediate (V) or from the acid (IV) using a one pot procedure). Finally, target compounds were easily prepared by basic hydrolysis of the 2-carboxyethyl ester protecting group.

1 Struys, M.M.R.F.; et al.; Tetrahedron 1993, 49, 10, 2239.
2 Davison, S.C.; et al.; VCH Publichers: Stuttgart 1989, 147, 4, 972-6.
3 Di Fabio, R.; Cugola, A.; Donati, D.; Ferinai, A.; Gaviraghi, G.; Ratti, E.; Trist, D.G.; Reggiani, A.; Identification and pharmacological characterization of GV150526, a novel glycine antagonist as potent neuroprotective agent. Drugs Fut 1998, 23, 1, 61.
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) 28066 1-(3,5-dichlorophenyl)hydrazine 39943-56-1 C6H6Cl2N2 详情 详情
(II) 17491 ethyl acetate 141-78-6 C4H8O2 详情 详情
(III) 32141 ethyl 2-[(E)-2-(3,5-dichlorophenyl)hydrazono]propanoate C11H12Cl2N2O2 详情 详情
(IV) 32142 ethyl 4,6-dichloro-1H-indole-2-carboxylate C11H9Cl2NO2 详情 详情
(V) 32143 N-methyl-N-phenylacetamide 579-10-2 C9H11NO 详情 详情
(VI) 32144 ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate C12H9Cl2NO3 详情 详情
(VII) 32145 N-phenyl-2-(triphenylphosphoranylidene)acetamide C26H22NOP 详情 详情
(VIII) 32147 ethyl 3-[(E)-3-anilino-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate C20H16Cl2N2O3 详情 详情
Extended Information