-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[4-[Bis(2-chloroethyl)amino]phenyl]-N'-[2-(4-hydroxyphenyl)ethyl]urea

【CA登记号】393511-88-1

【分子式】C₁₉H₂₃Cl₂N₃O₂

【分子量】396.32006

【开发单位】Imperial Coll. of Sci., Technol. & Med. (Originator), University of Reading (Originator)

【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Melanoma Therapy, Oncolytic Drugs, Nitrogen Mustards

合成路线1 合成路线2 合成路线3

合成路线1

Coupling of tyramine (I) with p-nitrophenyl isocyanate (II) affords urea (III). Subsequent nitro group reduction with H2 and Pd/C gives amine (IV). Condensation of amine (IV) with ethylene oxide (V) leads to the bis-hydroxyethyl amine (VI). This is finally chlorinated employing SOCl2 in pyridine. Alternatively, amine (IV) is subjected to reductive alkylation with chloroacetaldehyde and NaBH3CN to furnish the target bis-chloroethyl amine. (1,2)

参考文献中间体

【1】 Jordan, A.M.; Khan, T.H.; Malkin, H.; Osborn, H.M.I.; Synthesis and analysis of urea and carbamate prodrugs as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). Bioorg Med Chem 2002, 10, 8, 2625.
【2】 Riley, P.A.; Photiou, A.; Khan, T.H.; Osborn, H.M.I.; Malkin, H.; Phenylethylamine derivs. and their use in the treatment of melanoma. EP 1303481; WO 0208174 .

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)	19988	4-(2-Aminoethyl)phenol; Tyramine	51-67-2	C₈H₁₁NO	详情	详情
(II)	14909	1-isocyanato-4-nitrobenzene; 4-Nitrophenyl isocyanate	100-28-7	C₇H₄N₂O₃	详情	详情
(III)	64077	N-(4-hydroxyphenethyl)-N'-(4-nitrophenyl)urea		C₁₅H₁₅N₃O₄	详情	详情
(IV)	64078	N-(4-aminophenyl)-N'-(4-hydroxyphenethyl)urea		C₁₅H₁₇N₃O₂	详情	详情
(V)	10393	Oxirane; Ethylene oxide	75-21-8	C₂H₄O	详情	详情
(VI)	64079	N-{4-[bis(2-hydroxyethyl)amino]phenyl}-N'-(4-hydroxyphenethyl)urea		C₁₉H₂₅N₃O₄	详情	详情

合成路线2

In an alternative method, p-nitroaniline (I) is reacted with ethylene oxide (II) to afford diol (III). This compound can also be prepared by condensation of 1-fluoro-4-nitrobenzene (IV) with diethanolamine (V). Chlorination of diol (III) to provide (VI) is accomplished with either mesyl chloride or SOCl2 in the presence of pyridine. Then, nitro group reduction in (VI) by means of iron and HCl affords aniline (VII).

参考文献中间体

【1】 Jordan, A.M.; Khan, T.H.; Malkin, H.; Osborn, H.M.I.; Synthesis and analysis of urea and carbamate prodrugs as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). Bioorg Med Chem 2002, 10, 8, 2625.

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)	15547	4-nitrophenylamine; p-Nitroaniline; 4-nitroaniline	100-01-6	C₆H₆N₂O₂	详情	详情
(II)	10393	Oxirane; Ethylene oxide	75-21-8	C₂H₄O	详情	详情
(III)	64080	2-[(2-hydroxyethyl)-4-nitroanilino]-1-ethanol		C₁₀H₁₄N₂O₄	详情	详情
(IV)	14153	4-Fluoronitrobenzene; 1-Fluoro-4-nitrobenzene	350-46-9	C₆H₄FNO₂	详情	详情
(V)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情
(VI)	64081	N,N-bis(2-chloroethyl)-4-nitroaniline; N,N-bis(2-chloroethyl)-N-(4-nitrophenyl)amine		C₁₀H₁₂Cl₂N₂O₂	详情	详情
(VII)	64082	N~1~,N~1~-bis(2-chloroethyl)-1,4-benzenediamine; N-(4-aminophenyl)-N,N-bis(2-chloroethyl)amine		C₁₀H₁₄Cl₂N₂	详情	详情

合成路线3

Reaction of tyramine (VIII) with p-nitrophenyl chloroformate (IX) gives rise to the nitrophenyl carbamate (X). Finally, coupling of (X) with aniline (VII) provides the title urea.

参考文献中间体

【1】 Jordan, A.M.; Khan, T.H.; Malkin, H.; Osborn, H.M.I.; Synthesis and analysis of urea and carbamate prodrugs as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). Bioorg Med Chem 2002, 10, 8, 2625.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	64082	N~1~,N~1~-bis(2-chloroethyl)-1,4-benzenediamine; N-(4-aminophenyl)-N,N-bis(2-chloroethyl)amine		C₁₀H₁₄Cl₂N₂	详情	详情
(VIII)	19988	4-(2-Aminoethyl)phenol; Tyramine	51-67-2	C₈H₁₁NO	详情	详情
(IX)	16605	4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene	7693-46-1	C₇H₄ClNO₄	详情	详情
(X)	64083	4-nitrophenyl 4-hydroxyphenethylcarbamate		C₁₅H₁₄N₂O₅	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)