(1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione -Drug Synthesis Database

【结构式】

【分子编号】11174

【品名】(1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione

【CA登记号】

【分子式】C₁₃H₁₈BrNO₂

【分子量】300.19546

【元素组成】C 52.01% H 6.04% Br 26.62% N 4.67% O 10.66%

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：(IV)

New syntheses of tandospirone have been described: 1) The hydrogenation of bicyclo[2.2.1]hept-5-ene-2,3-di-exo-carboxylic acid anhydride (I) with H2 over Pd/C in THF-water gives bicyclo[2.2.1]heptane-2,3-di-exo-carboxylic acid anhydride (II), which by reaction with ammonia in THF-water is converted into the imide (III). The reaction of (III) with 1,4-dibromobutane by means of K2CO3 in refluxing acetone yields N-(4-bromobutyl)bicyclo[2.2.1]heptane-2,3-di-exo-carboximide (IV), which is finally condensed with 1-(2-pyrimidinyl)piperazine (V) by means of K2CO3 and KI in hot DMF. 2) Imide (III) is condensed with propargyl bromide (VI) by means of K2CO3 in refluxing acetone affording N-propargylbicyclo[2.2.1]heptane-2,3-di-exo-carboximide (VII), which is allowed to react with piperazine (V) and formaldehyde by means of CuSO4 in dioxane to give N-[4-[4-(2-pyrimidinyl)piperazin-1-yl]-2-butynyl]bicyclo[2.2.1]heptane-2,3-di-exo-carboximide (VIII). Finally, this compound is reduced with H2 over Pd/C. 3) The condensation of piperazine (V) with 4-chlorobutyronitrile (IX) by means of NaOH in acetone gives 4-[4-(2-pyrimidinyl)piperazin-1-yl]butyronitrile (X), which is reduced with LiAlH4 in ether yielding 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (XI). Finally, this compound is condensed with anhydride (II) in refluxing pyridine.

参考文献中间体

合成目标

【1】 Kojima, A.; Ishizumi, K.; Antoku, F.; Synthesis and anxiolytic activity of N-substituted cyclic imides (1R,2S,3R,4S)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3-bicyclo[2.2.1]heptanedicarboximide (tandospirone) and related compounds. Chem Pharm Bull 1991, 39, 9, 2288.

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)	11171	(1R,2R,6S,7S)-4-Oxatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₈O₃	详情	详情
(II)	11172	(1R,2S,6R,7S)-4-Oxatricyclo[5.2.1.0(2,6)]decane-3,5-dione	6004-79-1	C₉H₁₀O₃	详情	详情
(III)	11173	(1R,2S,6R,7S)-4-Azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₉H₁₁NO₂	详情	详情
(IV)	11174	(1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₃H₁₈BrNO₂	详情	详情
(V)	11175	2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine	20980-22-7	C₈H₁₂N₄	详情	详情
(VI)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(VII)	11177	(1R,2S,6R,7S)-4-(2-Propynyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₂H₁₃NO₂	详情	详情
(VIII)	11178	(1R,2S,6R,7S)-4-[4-[4-(2-Pyrimidinyl)piperazino]-2-butynyl]-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₂₁H₂₅N₅O₂	详情	详情
(IX)	11179	4-Chlorobutanenitrile; 4-Chlorobutyronitrile	628-20-6	C₄H₆ClN	详情	详情
(X)	11180	4-[4-(2-Pyrimidinyl)piperazino]butanenitrile		C₁₂H₁₇N₅	详情	详情
(XI)	11181	4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine	33386-20-8	C₁₂H₂₁N₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The synthesis of SM-3997 labeled in the carbonyl groups or the pyrimidine ring has been reported: The Diels-Alder condensation of cyclopentadiene (II) with [14C]-labeled maleic anhydride (I) gives bicyclo[2.2.1]hept-5-ene-2,3-endo-di[14C]-carboxylic anhydride (III), which by treatment with ammonia in THF is converted to the corresponding imide (IV endo). Heating of (IV endo) at 190 C in diphenylether affords the corresponding exo isomer (IV exo), which is hydrogenated with H2 over Pd/C in ethanol - THF to give the saturated exo-imide (V). The condensation of (V) with 1,4-dibromobutane (VI) by means of K2CO3 in refluxing acetone yields the N-(4-bromobutyl)imide (VII), which is finally condensed with 1-(2-pyrimidinyl)piperazine (VIII) by means of K2CO3 and KI in hot DMF to afford SM-399 [14C]-labeled at the carbonyl groups.

参考文献中间体

合成目标

【1】 Kanamaru, H.; Nishioka, K.; 14C-labeling of a novel anxiolytic agent tandospirone. J Label Compd Radiopharm 1992, 31, 6, 427.

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 endo)	11185	(1R,2S,6R,7S)-4-Azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₉NO₂	详情	详情
(IV exo)	11186	(1R,2R,6S,7S)-4-Azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₉NO₂	详情	详情
(IV endo)	45052	(1R,2R,6S,7S)-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₉NO₂	详情	详情
(IV exo)	45053	(1R,2S,6R,7S)-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₉NO₂	详情	详情
(I)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(I)	45050	2,5-furandione		C₄H₂O₃	详情	详情
(II)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(III)	11184	(1R,2S,6R,7S)-4-Oxatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₈O₃	详情	详情
(III)	45051	(1R,2R,6S,7S)-4-oxatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₉H₈O₃	详情	详情
(V)	11173	(1R,2S,6R,7S)-4-Azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₉H₁₁NO₂	详情	详情
(V)	45054	(1R,2R,6S,7S)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₉H₁₁NO₂	详情	详情
(VII)	11174	(1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₃H₁₈BrNO₂	详情	详情
(VII)	45055	(1R,2R,6S,7S)-4-(4-bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₃H₁₈BrNO₂	详情	详情
(VIII)	11175	2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine	20980-22-7	C₈H₁₂N₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The condensation of piperazine (I) with [14C]-labeled 2-chloropyrimidine (II) in refluxing ethanol gives the labeled 1-(2-pyrimidinyl)piperazine (III), which is then condensed with the N-(4-bromobutyl)imide (IV) by means of K2CO3 and KI as before, affording SM-3997 labeled at the pyrimidine ring.

参考文献中间体

合成目标

【1】 Kanamaru, H.; Nishioka, K.; 14C-labeling of a novel anxiolytic agent tandospirone. J Label Compd Radiopharm 1992, 31, 6, 427.

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)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(II)	11191	2-Chloropyrimidine	1722-12-9	C₄H₃ClN₂	详情	详情
(II)	45056	2-chloropyrimidine		C₄H₃ClN₂	详情	详情
(III)	11175	2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine	20980-22-7	C₈H₁₂N₄	详情	详情
(III)	45057	2-(1-piperazinyl)pyrimidine		C₈H₁₂N₄	详情	详情
(IV)	11174	(1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₁₃H₁₈BrNO₂	详情	详情

Extended Information