Dichlorophoephoric acid 4-bromophenyl ester -Drug Synthesis Database

【结构式】

【分子编号】25314

【品名】Dichlorophoephoric acid 4-bromophenyl ester

【CA登记号】

【分子式】C₆H₄BrCl₂O₂P

【分子量】289.879722

【元素组成】C 24.86% H 1.39% Br 27.56% Cl 24.46% O 11.04% P 10.69%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

Treatment of 4-bromophenol (I) with phosphoryl chloride gave p-bromophenyl phosphoro- dichloridate (II), which was condensed with alanine methyl ester (III) to furnish alaninyl phosphorochloridate (IV). Further coupling of (IV) with 3'-azidothimidine (V) in the presence of N-methylimidazole afforded phosphate (VI). Then, addition of methyl hypobromite, (prepared from bromine and MeOH) provided the title compound as a diastereomeric mixture.

参考文献中间体

合成目标

【1】 D'Cruz, O.; Jan, S.-T.; Shih, M.-J.; Chen, C.-L.; Uckun, F.M.; Venkatachalam, T.K.; Synthesis of dual function (5R,6R)- and (5S,6S)-5-bromo-6-methoxy-5,6-dihydro-AZT-5'-(para-bromophenyl methoxyalaninyl phosphate) as novel spermicidal and anti-HIV agents. Antivir Chem Chemother 1999, 10, 1, 39.
【2】 Uckun, F.M.; Venkatachalam, T.; D'Cruz, O. (Parker Hughes Institute); AZT derivs. exhibiting spermicidal and anti-viral activity. WO 9948902 .

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	25314	Dichlorophoephoric acid 4-bromophenyl ester		C₆H₄BrCl₂O₂P	详情	详情
(III)	25315	methyl 2-aminopropanoate; Alanine, methyl ester	7625-53-8	C₄H₉NO₂	详情	详情
(IV)	25316	methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate		C₁₀H₁₂BrClNO₄P	详情	详情
(V)	25317	1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	101703-35-9	C₁₀H₁₃N₅O₄	详情	详情
(VI)	25318	methyl 2-[[[((2S,3S,5R)-3-azido-5-[[(propionylamino)carbonyl]amino]tetrahydro-2-furanyl)methoxy](4-bromophenoxy)phosphoryl]amino]propanoate		C₂₀H₂₄BrN₆O₈P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The intermediate phosphorochloridate (III) has been obtained as follows: The reaction of 4-bromophenol (IV) with POCl3 and triethylamine in ethyl ether gives the corresponding phosphorodichloridate (V), which is finally condensed with L-alanine methyl ester (VI) by means of triethylamine in dichloromethane.

参考文献中间体

合成目标

【1】 Uckun, F.M. (Parker Hughes Institute); Aryl phosphate derivatives of d4T having anti-HIV activity. WO 0000501 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	32793	methyl (2S)-2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate		C₁₀H₁₂BrClNO₄P	详情	详情
(IV)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(V)	25314	Dichlorophoephoric acid 4-bromophenyl ester		C₆H₄BrCl₂O₂P	详情	详情
(VI)	20694	methyl (2S)-2-aminopropanoate		C₄H₉NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Treatment of p-bromophenol (I) with phosphoryl chloride and triethylamine furnished p-bromophenyl phosphorodichloridate (II), which was condensed with alanine methyl ester (III) to give the intermediate phosphorochloridate (IV). Then, coupling of chloridate (IV) with azidothimidine (V) in the presence of N-methylimidazole yielded the title compound.

参考文献中间体

合成目标

【1】 Venkatachalam, T.K.; Zhu, Z.; Shih, M.-J.; Tai, H.-L.; Uckun, F.M.; Jan, S.-T.; AZT-5'-(p-bromophenyl methoxyalaninyl phosphate) as a potent and non-toxic anti-human immunodeficiency virus agent. Antivir Chem Chemother 1999, 10, 1, 47.

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	25314	Dichlorophoephoric acid 4-bromophenyl ester		C₆H₄BrCl₂O₂P	详情	详情
(III)	25315	methyl 2-aminopropanoate; Alanine, methyl ester	7625-53-8	C₄H₉NO₂	详情	详情
(IV)	25316	methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate		C₁₀H₁₂BrClNO₄P	详情	详情
(V)	25317	1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	101703-35-9	C₁₀H₁₃N₅O₄	详情	详情

Extended Information