methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-2-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】50997

【品名】methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-2-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate

【CA登记号】

【分子式】C₃₁H₅₁NO₂Sn

【分子量】588.46148

【元素组成】C 63.27% H 8.74% N 2.38% O 5.44% Sn 20.17%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IX)

Conjugate addition of tolylmagnesium bromide (II) to ecgonidine methyl ester (I) provided the 3-beta-tolyl tropane derivative (III). N-Dealkylation of (III) to produce the nortropane analogue (V) was carried out via acylation with trichloroethyl chloroformate, followed by reductive cleavage of the resultant trichloroethyl carbamate (IV) with Zn and HOAc. Alkylation of the secondary amine (V) with propargyl bromide (VI) afforded the corresponding propargyl amine (VII). Subsequent hydrostannylation of the propargyl group furnished the desired (E)-stannylpropenyl compound (VIII) along with the corresponding (Z)-isomer. In an improved procedure, amine (V) was alkylated with (E)-3-chloro-1-(tributylstannyl)-1-propene (IX) to yield pure (VIII). Finally, the title vinyl iodide was obtained by iododestannylation of (VIII) employing iodine in cold CHCl3.

参考文献中间体

合成目标

【1】 Emond, P.; et al.; Synthesis and ligand bindin of nortropane derivatives: N-substituted 2beta-carbomethoxy-3beta-(4'-iodophenyl)nortropane and N-(3-iodotrop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3',4'-disubstituted phenyl)nortropane. New high-affinity and selective compounds. J Med Chem 1997, 40, 9, 1366.
【2】 Mauclaire, L.; Edmond, P.; Guilloteau, D.; Besnard, J.-C.; Frangin, Y. (CIS Bio International); Tropane derivs. useable in particular for in vivo detection of dopamine transporters. EP 0901491; JP 2000510141; US 6180083; WO 9743285 .

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)	35657	bromo(4-methylphenyl)magnesium	4294-57-9	C₇H₇BrMg	详情	详情
(III)	50267	methyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₇H₂₃NO₂	详情	详情
(IV)	50993	2-methyl 8-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate		C₁₉H₂₂Cl₃NO₄	详情	详情
(V)	50994	methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₆H₂₁NO₂	详情	详情
(VI)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(VII)	50995	tributyl[(E)-3-chloro-1-propenyl]stannane		C₁₅H₃₁ClSn	详情	详情
(VIII)	50996	methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-(2-propynyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₉H₂₃NO₂	详情	详情
(IX)	50997	methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-2-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate		C₃₁H₅₁NO₂Sn	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of the tributystannyl derivative (I) with 123INa and H2O2 in ethanol yields the target radiolabelled compound.

参考文献中间体

合成目标

【1】 Berthommier, E.; et al.; New preparation of [123I]PE2I: Investigation of the oxidation and purification steps. J. Label. Comp. and Radiopharm. 2002, 45, 12, 1019.

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)	50997	methyl (1R,2S,3S,5S)-3-(4-methylphenyl)-8-[(E)-3-(tributylstannyl)-2-propenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate		C₃₁H₅₁NO₂Sn	详情	详情

Extended Information