1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione -Drug Synthesis Database

【结构式】

【分子编号】53533

【品名】1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione

【CA登记号】19844-27-0

【分子式】C₁₀H₅Cl₂NO₂

【分子量】242.06064

【元素组成】C 49.62% H 2.08% Cl 29.29% N 5.79% O 13.22%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(VII)

The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II), which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV). The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords the title product as a mixture of two diastereomeric racemates that are separated by column chromatography.

参考文献中间体

合成目标

【2】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Condensed imidazolidinones as tRNA synthetase inhibitors. WO 0018772 .
【1】 Hill, J.M.; Oliver, N.; Yu, X.; Wang, Z.; Finn, J.; Silverman, J.; Gallant, P.; Wendler, P.; Keith, D.; Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1707.

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)	53530	1,3-Diketohydrindene; 1,3-Indandione; 1,3-Indanedione	606-23-5	C₉H₆O₂	详情	详情
(II)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(III)	53531	2-Benzylidene-1,3-indandione	n/a	C₁₆H₁₀O₂	详情	详情
(IV)	53532		n/a	C₁₆H₁₀O₃	详情	详情
(V)	23629	3,4-dichloroaniline	95-76-1	C₆H₅Cl₂N	详情	详情
(VI)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(VII)	53533	1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione	19844-27-0	C₁₀H₅Cl₂NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【2】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Condensed imidazolidinones as tRNA synthetase inhibitors. WO 0018772 .
【1】 Hill, J.M.; Oliver, N.; Yu, X.; Wang, Z.; Finn, J.; Silverman, J.; Gallant, P.; Wendler, P.; Keith, D.; Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1707.

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)	53530	1,3-Diketohydrindene; 1,3-Indandione; 1,3-Indanedione	606-23-5	C₉H₆O₂	详情	详情
(II)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(III)	53531	2-Benzylidene-1,3-indandione	n/a	C₁₆H₁₀O₂	详情	详情
(IV)	53532		n/a	C₁₆H₁₀O₃	详情	详情
(V)	53533	1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione	19844-27-0	C₁₀H₅Cl₂NO₂	详情	详情
(VI)	23629	3,4-dichloroaniline	95-76-1	C₆H₅Cl₂N	详情	详情
(VII)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (II), which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV). The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3). Finally, (VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.

参考文献中间体

合成目标

【1】 Hill, J.M.; Oliver, N.; Yu, X.; Wang, Z.; Finn, J.; Silverman, J.; Gallant, P.; Wendler, P.; Keith, D.; Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1707.
【2】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Tetracyclic heterocycles as antimicrobial agents. US 6153645; WO 0017206 .
【3】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Condensed imidazolidinones as tRNA synthetase inhibitors. WO 0018772 .

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)	53530	1,3-Diketohydrindene; 1,3-Indandione; 1,3-Indanedione	606-23-5	C₉H₆O₂	详情	详情
(II)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(III)	53531	2-Benzylidene-1,3-indandione	n/a	C₁₆H₁₀O₂	详情	详情
(IV)	53532		n/a	C₁₆H₁₀O₃	详情	详情
(V)	53533	1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione	19844-27-0	C₁₀H₅Cl₂NO₂	详情	详情
(VI)	23629	3,4-dichloroaniline	95-76-1	C₆H₅Cl₂N	详情	详情
(VII)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(VIII)	53598		n/a	C₂₆H₁₅Cl₂NO₅	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

The condensation of indane-1,3-dione (I) with benzaldehyde (II) by means of piperidine in refluxing benzene gives 2-benzylideneindane-1,3-dione (III), which is treated with H2O2 and NaOH in methanol to yield the epoxide (IV). The condensation of (IV) with N-(3,4-dichlorophenyl)maleimide (V) (obtained by condensation of 3,4-dichloroaniline (VI) with maleic anhydride (VII) in diethyl ether) in refluxing benzene affords a mixture of two diastereomeric racemates from which the desired isomer (VIII) is separated by column chromatography (1-3). Finally, (VIII) is reduced with NaBH4 in methanol to provide a diastereomeric mixture from which the title product is separated by chromatography.

参考文献中间体

合成目标

【1】 Hill, J.M.; Oliver, N.; Yu, X.; Wang, Z.; Finn, J.; Silverman, J.; Gallant, P.; Wendler, P.; Keith, D.; Synthesis and activity of spirocyclic tetrahydrofurans as inhibitors of phenylalanine tRNA synthetase. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1707.
【2】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Condensed imidazolidinones as tRNA synthetase inhibitors. WO 0018772 .
【3】 Wang, Z.; Hill, J.; Finn, J.; Yu, X.Y.; Keith, D.; Gallant, P.; Wendler, P. (Cubist Pharmaceuticals, Inc.); Tetracyclic heterocycles as antimicrobial agents. US 6153645; WO 0017206 .

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)	53530	1,3-Diketohydrindene; 1,3-Indandione; 1,3-Indanedione	606-23-5	C₉H₆O₂	详情	详情
(II)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(III)	53531	2-Benzylidene-1,3-indandione	n/a	C₁₆H₁₀O₂	详情	详情
(IV)	53532		n/a	C₁₆H₁₀O₃	详情	详情
(V)	53533	1-(3,4-dichlorophenyl)-1H-pyrrole-2,5-dione	19844-27-0	C₁₀H₅Cl₂NO₂	详情	详情
(VI)	23629	3,4-dichloroaniline	95-76-1	C₆H₅Cl₂N	详情	详情
(VII)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(VIII)	53598		n/a	C₂₆H₁₅Cl₂NO₅	详情	详情

Extended Information