-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】3exo-(4-Bromophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1]octane-2exo-carboxylic acid methyl ester

【CA登记号】

【分子式】C₁₈H₂₃BrFNO₂

【分子量】384.29191

【开发单位】McLean Hospital (Originator), Natural Pharmacia (Originator)

【药理作用】DIAGNOSTIC AGENTS, Dopamine Transporter (DAT) Inhibitors

合成路线1

Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Bromodesilylation of (III) using NaBr and N-chlorosuccinimide gave the bromophenyl derivative (IV). Amine demethylation was accomplished by reaction of (IV) with 1-chloroethyl chloroformate, followed by hydrolysis and decarboxylation of the intermediate carbamate (V) upon treatment with methanol. The resulting secondary amine (VI) was then alkylated with 3-fluoropropyl bromide (VII) to furnish the title fluoropropyl amine.

参考文献中间体

【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.

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)	21118	methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate		C₁₀H₁₅NO₂	详情	详情
(II)	50257	bromo[4-(trimethylsilyl)phenyl]magnesium		C₉H₁₃BrMgSi	详情	详情
(III)	50258	methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₉H₂₉NO₂Si	详情	详情
(IV)	50264	methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₆H₂₀BrNO₂	详情	详情
(V)	50265	8-(1-chloroethyl) 2-methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate		C₁₈H₂₁BrClNO₄	详情	详情
(VI)	50266	methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₅H₁₈BrNO₂	详情	详情
(VII)	19812	1-bromo-3-fluoropropane	352-91-0	C₃H₆BrF	详情	详情

Extended Information