methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate -Drug Synthesis Database

【结构式】

【分子编号】25316

【品名】methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate

【CA登记号】

【分子式】C₁₀H₁₂BrClNO₄P

【分子量】356.540082

【元素组成】C 33.69% H 3.39% Br 22.41% Cl 9.94% N 3.93% O 17.95% P 8.69%

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：(IV)

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：(IV)

In a related procedure, methyl hypobromite was added to 3'-azidothimidine (V) in MeOH, and the resulting mixture of diastereomeric 5-bromo-6-methoxypyrimidines (VII) and (VIII) was separated by column chromatography. Both the (5R,6R)- and the (5S,6S)-isomers (VII) and (VIII) were then coupled to phosphorochloridate (IV) to yield the title compound as seperated enantiomers.

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
(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
(VII)	25319	(5R,6R)-1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-bromo-6-methoxy-5-methyldihydro-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₆BrN₅O₅	详情	详情
(VIII)	25320	(5S,6S)-1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-bromo-6-methoxy-5-methyldihydro-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₆BrN₅O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The dehydration of thymidine (I) by known methods (J Med Chem 1989, 32: 461) gives 2,3-anhydrothymidine (II), which is then esterifired with the phosphoryl chloride (III) by means of 1-methylimidazole in THF.

参考文献中间体

合成目标

【1】 Vig, R.; Venkatachalam, T.K.; Uckun, F.M.; D4T-5'-[p-Bromophenyl methoxyalaninyl phosphate] as a potent and non-toxic anti-human immunodeficiency virus agent. Antivir Chem Chemother 1998, 9, 5, 445.
【2】 Venkatachalam, T.K.; Tai, H.-L.; Vig, R.; Chen, C.-L.; Jan, S.-T.; Uckun, F.M.; Enhancing effects of a mono-bromo substitution at the para position of the phenyl moiety on the metabolism and anti-HIV activity of d4T-phenyl methoxyalaninyl phosphate derivatives. Bioorg Med Chem Lett 1998, 8, 22, 3121.

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)	12161	Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	50-89-5	C₁₀H₁₄N₂O₅	详情	详情
(II)	25323	1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione		C₁₀H₁₂N₂O₄	详情	详情
(III)	25316	methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate		C₁₀H₁₂BrClNO₄P	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

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