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【结 构 式】 
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【分子编号】34465 【品名】N-[(1S)-1-phenylethyl]-N-[(3R)pyrrolidinylmethyl]amine; (1S)-1-phenyl-N-[(3R)pyrrolidinylmethyl]-1-ethanamine 【CA登记号】 |
【 分 子 式 】C13H20N2 【 分 子 量 】204.31528 【元素组成】C 76.42% H 9.87% N 13.71% |
合成路线1
该中间体在本合成路线中的序号：(VI)Hydrogenation of the enantiomerically pure 1-(alpha-methylbenzyl)-3-(hydroxymethyl)pyrrolidine (I) in the presence of Pearlman's catalyst and di-tert-butyl dicarbonate produced the N-Boc pyrrolidine (II). Reaction of (II) with methanesulfonyl chloride, followed by condensation of the resulting mesylate (III) with (S)-alpha-methylbenzylamine (IV) in toluene at 150 C in a sealed tube afforded the aminomethyl pyrrolidine derivative (V). Then, acidic cleavage of the Boc protecting group yielded pyrrolidine (VI).
| 【1】 Sternfeld, F.; Guiblin, A.R.; Jelley, R.A.; et al.; Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: Potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor. J Med Chem 1999, 42, 4, 677. |
| 【2】 Ogawa, T.; Terai, T.; Haruna, K.; Watanabe, A.; Tominaga, T.; Taguchi, H. (Senju Pharmaceuticals Co., Ltd.; Toyobo Co., Ltd.); Pharmaceutical compsn. for topical administration to the eye for treating allergic conjunctivitis. CA 2165999; EP 0719553; JP 1996231393 . |
| 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) | 34461 | [(3R)-1-[(1R)-1-phenylethyl]pyrrolidinyl]methanol | C13H19NO | 详情 | 详情 | |
| (II) | 34462 | tert-butyl (3R)-3-(hydroxymethyl)-1-pyrrolidinecarboxylate | C10H19NO3 | 详情 | 详情 | |
| (III) | 34463 | 1-Boc-3-methanesulfonyloxymethylpyrrolidine; 1-Boc-3-methanesulfonyloxymethylpyrrolidine | 141699-56-1 | C11H21NO5S | 详情 | 详情 |
| (IV) | 20042 | (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine | C8H11N | 详情 | 详情 | |
| (V) | 34464 | tert-butyl (3S)-3-([[(1S)-1-phenylethyl]amino]methyl)-1-pyrrolidinecarboxylate | C18H28N2O2 | 详情 | 详情 | |
| (VI) | 34465 | N-[(1S)-1-phenylethyl]-N-[(3R)pyrrolidinylmethyl]amine; (1S)-1-phenyl-N-[(3R)pyrrolidinylmethyl]-1-ethanamine | C13H20N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Halogenation of the substituted aniline (VII) by means of iodine monochloride gave ortho-iodoaniline (VIII). 3-Butyn-1-ol (IX) was protected as the 1,4-bis(triethylsilyl)derivative (X) by deprotonation with butyllithium, followed by treatment with triethylsilyl chloride. Palladium-catalyzed condensation of disilylated butynol (X) with iodoaniline (VIII) furnished a mixture of the bis(silylated) tryptophol (XI) and the O-desilylated analogue (XII). Treatment of the crude mixture with methanolic HCl produced the completely desilylated indole (XIII), which was converted to mesylate (XIV) by reaction with methanesulfonyl chloride and triethylamine. Alkylation of pyrrolidine (VI) with mesylate (XIV) then yielded the target (indolylethyl)pyrrolidine, which was finally converted to the title dioxalate salt.
| 【1】 Sternfeld, F.; Guiblin, A.R.; Jelley, R.A.; et al.; Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: Potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor. J Med Chem 1999, 42, 4, 677. |
| 【2】 Ogawa, T.; Terai, T.; Haruna, K.; Watanabe, A.; Tominaga, T.; Taguchi, H. (Senju Pharmaceuticals Co., Ltd.; Toyobo Co., Ltd.); Pharmaceutical compsn. for topical administration to the eye for treating allergic conjunctivitis. CA 2165999; EP 0719553; JP 1996231393 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 34465 | N-[(1S)-1-phenylethyl]-N-[(3R)pyrrolidinylmethyl]amine; (1S)-1-phenyl-N-[(3R)pyrrolidinylmethyl]-1-ethanamine | C13H20N2 | 详情 | 详情 | |
| (VI) | 34470 | 2-(5-[[(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl]-1H-indol-3-yl)ethyl methanesulfonate | C15H18N2O5S | 详情 | 详情 | |
| (VII) | 15345 | (4S)-4-(4-aminobenzyl)-1,3-oxazolan-2-one | C10H12N2O2 | 详情 | 详情 | |
| (VIII) | 34466 | (4S)-4-(4-amino-3-iodobenzyl)-1,3-oxazolidin-2-one | C10H11IN2O2 | 详情 | 详情 | |
| (IX) | 32507 | 3-butyn-1-ol | 927-74-2 | C4H6O | 详情 | 详情 |
| (X) | 16862 | triethylsilyl 4-(triethylsilyl)-3-butynyl ether; triethyl[[4-(triethylsilyl)-3-butynyl]oxy]silane | 160194-28-5 | C16H34OSi2 | 详情 | 详情 |
| (XI) | 34467 | (4S)-4-[(2-(triethylsilyl)-3-[2-[(triethylsilyl)oxy]ethyl]-1H-indol-5-yl)methyl]-1,3-oxazolidin-2-one | C26H44N2O3Si2 | 详情 | 详情 | |
| (XII) | 34468 | (4S)-4-[[3-(2-hydroxyethyl)-2-(triethylsilyl)-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one | C20H30N2O3Si | 详情 | 详情 | |
| (XIII) | 34469 | (4S)-4-[[3-(2-hydroxyethyl)-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one | C14H16N2O3 | 详情 | 详情 |