3-phenylpyrrolidine -Drug Synthesis Database

【结构式】

【分子编号】30991

【品名】3-phenylpyrrolidine

【CA登记号】

【分子式】C₁₀H₁₃N

【分子量】147.21996

【元素组成】C 81.59% H 8.9% N 9.51%

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：(IV)

This compound has been obtained by several different ways: 1) The reaction of 6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-one (I) with trimethylsilyl cyanide gives 8,9-dihydronaphtho[1,2-d][1,3]dioxole-6-carbonitrile (II), which is hydrogenated with NaBH4 and hydrolyzed with KOH yielding the carboxylic acid (III). The condensation of (III) with 3-phenylpyrrolidine (IV) by means of DCC in THF affords the acylated pyrrolidine (V), which is reduced with BH3 in THF giving intermediate (VI) as a mixture of the cis and trans racemic diastereomers. Finally, the reaction of this mixture with methanesulfonic acid yields the corresponding mixture of mesylates that is separated by crystallization to afford the target cis racemate. 2) The reduction of carbonitrile (II) with H2 over Raney-Ni gives the corresponding amine (VII), which is cyclized with 2-phenylsuccinic anhydride (VIII) to yield the succinamic acid derivative (IX). The cyclization of (IX) by means of acetyl chloride affords the succinimide (X) as a mixture of the cis and trans racemic diastereomers, which are separated by crystallization giving the cis racemate (cis)(X). Finally, this racemate is reduced with BH3.THF or BH3. Dimethyl sulfide and treated with methanesulfonic acid to afford the target compound. 3) The cyclization of amine (VII) with the dimesylate (XI) by means of DIEA in ethanol gives also the previously described mixture of the cis and trans racemic diastereomers (VI).

参考文献中间体

合成目标

【1】 Buckner, S.A.; Zelle, R.E.; Basha, F.Z.; Meyer, M.D.; Tietje, K.; Hancock, A.A.; de Bernardis, J.F.; Synthesis and phamacological characterization of ABT-200: a putative novel antidepressant combining potent alpha-2 antagonism with moderate ne uotake inhibition. Bioorg Med Chem Lett 1994, 4, 11, 1319-22.
【2】 Deshpande, M.N.; et al.; A scalable process for the novel antidepressant ABT-200. Org Process Res Dev 1998, 2, 6, 351.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(cis)(X)	33723	(3R)-3-phenyl-1-[(6R)-6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethyl]-2,5-pyrrolidinedione	C₂₂H₂₁NO₄	详情	详情
(I)	33715	8,9-dihydronaphtho[1,2-d][1,3]dioxol-6(7H)-one	C₁₁H₁₀O₃	详情	详情
(II)	33716	8,9-dihydronaphtho[1,2-d][1,3]dioxole-6-carbonitrile	C₁₂H₉NO₂	详情	详情
(III)	33717	6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxole-6-carboxylic acid	C₁₂H₁₂O₄	详情	详情
(IV)	30991	3-phenylpyrrolidine	C₁₀H₁₃N	详情	详情
(V)	33718	(3-phenyl-1-pyrrolidinyl)(6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-yl)methanone	C₂₂H₂₃NO₃	详情	详情
(VI)	33719	3-phenyl-1-(6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethyl)pyrrolidine	C₂₂H₂₅NO₂	详情	详情
(VII)	33724	6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethylamine; 6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethanamine	C₁₂H₁₅NO₂	详情	详情
(VIII)	33720	3-phenyldihydro-2,5-furandione	C₁₀H₈O₃	详情	详情
(IX)	33721	4-oxo-3-phenyl-4-[(6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethyl)amino]butyric acid	C₂₂H₂₃NO₅	详情	详情
(X)	33722	3-phenyl-1-(6,7,8,9-tetrahydronaphtho[1,2-d][1,3]dioxol-6-ylmethyl)-2,5-pyrrolidinedione	C₂₂H₂₁NO₄	详情	详情
(XI)	33725	2,9-dimethyl-2,9-dimethylene-5-phenyl-3,8-dioxa-2lambda(6),9lambda(6)-dithia-1,9-decadiene	C₁₆H₂₆O₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The sulfonylation of 1-benzylpyrrolidin-3-ol by means of mesyl or tosyl chlorides gives the corresponding sulfonates (II) or (III), which are condensed with the diphenyl cuprate lithium (IV) yielding 1-benzyl-3-phenylpyrrolidine (V). The debenzylation of (V) with ammonium formate over Pd/C in methanol affords 3-phenylpyrrolidine (VI), which is finally condensed with 2-(4-bromobutyl)-1,2-benzoisothiazol-3-one S,S-dioxide (VII) by means of triethylamine in acetonitrile.

参考文献中间体

合成目标

【1】 Lee, C.-H.; Ahn, K.H.; Lee, S.J.; Park, T.K.; Hong, C.Y.; N-Substituted-3-arylpyrrolidines: Potent and selective ligands at serotonin 1A receptor. Bioorg Med Chem Lett 1999, 9, 10, 1379.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13975	p-Toluenesulfonyl chloride;p-tosyl chloride;Toluene-4-sulfonyl chloride;4-Toluene sulfochloride;tosyl chloride; 4-Methylbenzenesulfonyl chloride	98-59-9	C₇H₇ClO₂S	详情	详情
(I)	22746	1-benzyl-3-pyrrolidinol		C₁₁H₁₅NO	详情	详情
(II)	30988	1-benzyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]pyrrolidine		C₁₄H₂₁NOS	详情	详情
(III)	30989	1-benzyl-3-pyrrolidinyl 4-methylbenzenesulfonate		C₁₈H₂₁NO₃S	详情	详情
(V)	30990	1-benzyl-3-phenylpyrrolidine		C₁₇H₁₉N	详情	详情
(VI)	30991	3-phenylpyrrolidine		C₁₀H₁₃N	详情	详情
(VII)	17043	2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione		C₁₁H₁₂BrNO₃S	详情	详情

Extended Information