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【结 构 式】 
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【分子编号】38880 【品名】1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C21H31NO6S 【 分 子 量 】425.54628 【元素组成】C 59.27% H 7.34% N 3.29% O 22.56% S 7.54% |
合成路线1
该中间体在本合成路线中的序号：(VI)Protection of 3-methyl-3-sulfanylbutanoic acid (I) by treatment with 2,4,6-trimethoxybenzyl alcohol (II) and trifluoroacetic acid produced the trimethoxybenzyl thioether (III). Subsequent coupling of (III) with ethyl isonipecotate (IV) using EDC and DMAP gave amide (V). The ethyl ester group of (V) was then hydrolyzed to carboxylic acid (VI) by means of ethanolic NaOH. This was then condensed with 4-[2-(dimethylamino)ethoxy]-2-methyl-5-isopropylphenol (VIII), prepared by basic hydrolysis of moxisylyte (VII), and the resulting ester (IX) was deprotected with trifluoroacetic acid to give thiol (X). Finally, S-nitrosation of (X) with tert-butyl nitrite, followed by treatment with succinic acid furnished the title compound.
| 【1】 Earl, R.A.; et al.; Nitrosylated alpha-adrenergic receptor antagonists as potential agents for the treatment of erectile dysfunction. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 239. |
| 【2】 Gaston, R.D.; Saenz de Tejada, I.; Schroeder, J.D.; Shelekhin, T.E.; Garvey, D.S.; Wang, T. (NitroMed Inc.); Nitrosated and nitrosylated alpha-adrenergic receptor antagonists, compsns. and methods of use. WO 0012075 . |
| 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) | 32947 | 3-methyl-3-sulfanylbutyric acid | C5H10O2S | 详情 | 详情 | |
| (II) | 38877 | (2,4,6-trimethoxyphenyl)methanol | C10H14O4 | 详情 | 详情 | |
| (III) | 38878 | 3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid | C15H22O5S | 详情 | 详情 | |
| (IV) | 17410 | Ethyl isonipecotate; ethyl 4-piperidinecarboxylate | 1126-09-6 | C8H15NO2 | 详情 | 详情 |
| (V) | 38879 | ethyl 1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylate | C23H35NO6S | 详情 | 详情 | |
| (VI) | 38880 | 1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylic acid | C21H31NO6S | 详情 | 详情 | |
| (VII) | 38875 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl acetate | C16H25NO3 | 详情 | 详情 | |
| (VIII) | 38876 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol | C14H23NO2 | 详情 | 详情 | |
| (IX) | 38881 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl 1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylate | C35H52N2O7S | 详情 | 详情 | |
| (X) | 38882 | 4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl 1-(3-methyl-3-sulfanylbutanoyl)-4-piperidinecarboxylate | C25H40N2O4S | 详情 | 详情 |