N-phenyl-2-(triphenylphosphoranylidene)acetamide -Drug Synthesis Database

【结构式】

【分子编号】32145

【品名】N-phenyl-2-(triphenylphosphoranylidene)acetamide

【CA登记号】

【分子式】C₂₆H₂₂NOP

【分子量】395.440582

【元素组成】C 78.97% H 5.61% N 3.54% O 4.05% P 7.83%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

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.

参考文献中间体

合成目标

【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：(VII)

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.

参考文献中间体

合成目标

【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