【结 构 式】 |
【分子编号】22746 【品名】1-benzyl-3-pyrrolidinol 【CA登记号】 |
【 分 子 式 】C11H15NO 【 分 子 量 】177.24624 【元素组成】C 74.54% H 8.53% N 7.9% O 9.03% |
合成路线1
该中间体在本合成路线中的序号:(VII)By cyclocondensation of 3-nitrobenzaldehyde (I) with methyl 3-aminocrotonate (II) and 1-benzyl-3-(acetoacetoxy)pyrrolidine (III) in refluxing isopropanol. The pyrrolidine (III) is obtained as follows: The condensation of 2-hydroxysuccinic acid (IV) with benzylamine (VI), which is reduced with LiAlH4 in dry THF yielding N-benzyl-3-hydroxypyrrolidine (VIII). Finally, this compound is condensed with diketene (VII) by means of sodium acetate at 80 C.
【1】 Tamazawa, K.; Takeuchi, M.; Arima, H.; Synthesis of 14C-and 2H-labeled (3S)-1-benzyl-3-py. J Label Compd Radiopharm 1988, 25, 2, 161. |
【2】 Kojima, T.; Takenaka, T. (Yamanouchi Pharmaceutical Co., Ltd.); 1,4-Dihydropyridine-3,5-dicarboxylic acid ester de. DE 2904552; US 4220649 . |
【3】 Prous, J.; Castaner, J.; YM-09730-5. Drugs Fut 1988, 13, 7, 634. |
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) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
(II) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
(III) | 22742 | 2-Oxobutyric acid 1-benzylpyrrolidin-3-yl ester | C15H19NO3 | 详情 | 详情 | |
(IV) | 22743 | Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid | 617-48-1 | C4H6O5 | 详情 | 详情 |
(V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
(VI) | 22745 | 1-Benzyl-3-hydroxypyrrolidine-2,5-dione | C11H11NO3 | 详情 | 详情 | |
(VII) | 22746 | 1-benzyl-3-pyrrolidinol | C11H15NO | 详情 | 详情 | |
(VIII) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 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 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.
【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 |
合成路线3
该中间体在本合成路线中的序号:(I)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 bis(4-fluorophenyl)cuprate lithium (IV) yielding 1-benzyl-3-(4-fluorophenyl) pyrrolidine (V). The debenzylation of (V) with ammonium formate over Pd/C in methanol affords 3-(4-fluorophenyl)pyrrolidine (VI), which is finally condensed with 2-(4-bromobutyl)-1,2-benzoisothiazol-3-one S,S-dioxide (VII) by means of triethylamine in acetonitrile.
【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 |
---|---|---|---|---|---|---|
(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) | 30992 | 1-benzyl-3-(4-fluorophenyl)pyrrolidine | C17H18FN | 详情 | 详情 | |
(VI) | 30993 | 3-(4-fluorophenyl)pyrrolidine | C10H12FN | 详情 | 详情 | |
(VII) | 17043 | 2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C11H12BrNO3S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号:(I)Treatment of 1-benzyl-3-hydroxypyrrolidine (I) with methanesulfonyl chloride in the presence of DMAP and Et3N affords mesylate (II). Subsequent displacement of the mesylate group of (II) with the diarylcuprate reagent generated from 4-fluorophenyllithium (III) and cuprous bromide gives the 3-aryl pyrrolidine (IV). The N-benzyl group of (IV) is then removed by transfer hydrogenolysis with ammonium formate and Pd/C, yielding the secondary amine (V). This is finally alkylated with 2-(4-bromobutyl)-3-oxo-1,2-benzisothiazole 1,1-dioxide (VI) in the presence of Et3N in refluxing acetonitrile.
【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 |
---|---|---|---|---|---|---|
(I) | 22746 | 1-benzyl-3-pyrrolidinol | C11H15NO | 详情 | 详情 | |
(II) | 62833 | 1-benzyl-3-pyrrolidinyl methanesulfonate | C12H17NO3S | 详情 | 详情 | |
(III) | 62834 | (4-fluorophenyl)lithium | C6H4FLi | 详情 | 详情 | |
(IV) | 30992 | 1-benzyl-3-(4-fluorophenyl)pyrrolidine | C17H18FN | 详情 | 详情 | |
(V) | 30993 | 3-(4-fluorophenyl)pyrrolidine | C10H12FN | 详情 | 详情 | |
(VI) | 17043 | 2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C11H12BrNO3S | 详情 | 详情 |