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【结 构 式】 
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【分子编号】24297 【品名】1-(4-iodophenyl)-N-isopropyl-2-propanamine 【CA登记号】 |
【 分 子 式 】C12H18IN 【 分 子 量 】303.18613 【元素组成】C 47.54% H 5.98% I 41.86% N 4.62% |
合成路线1
该中间体在本合成路线中的序号：(V)1) Reductive amination of phenylacetone (I) with ammonium acetate and sodium cyanoborohydride (I) gives d,l-amphetamine (II), which is separated by distillation at reduced pressure from a secondary amine byproduct resulting from reaction of amphetamine with phenylacetone. Iodination of the N-acetyl-protected amine followed by acid hydrolysis yields a mixture of ortho-meta and para substituted iodoamphetamine, from which the para-isomer can be obtained by crystallization of the salt (IV) from hydrochloric acid. Reductive condensation of the primary amine salt with acetone and sodium cyanoborohydride then yields ofetamine (V). The free base is converted to the hydrochloride salt (VI) by treatment with dry HCl gas in ether. The acetate salt may be prepared by treatment of the free base with glacial acetic acid in ether, followed by addition of hexane or petroleum ether to precipitate the product.
| 【1】 Borch, R.F.; Durst, H.D.; Bernstein, M.D.; The cyanoborohydride anion as a selective reducing agent. J Am Chem Soc 1971, 93, 9, 2397. |
| 【2】 Lin, T.H.; Wu, J.L.; Baldwin, R.M.; Synthesis and brain uptake of isomeric I-123 iodoamphetamine derivatives. J Label Compd Radiopharm 1982, 19, 1305-1306. |
| 【3】 Baldwin, R.M.; Lin, T.H.; Wu, J.L.; Development of I-123 N-Isopropyl-p-iodoamphetamine: Exploration, synthesis, metabolism, toxicology, and radiation dosimetry. 16th Jpn Conf Rad Radioisotope (Dec 6-8, Tokio) 1983, 45, 23, 77. |
| 【4】 Donow, F.; Blanschke, G.; 1- Phenylethylaminderivative als optisch aktive Adsorbentien. Chem Ver 1975, 108, 2792. |
| 【5】 Baldwin, R.M.; Iofetamine (123I) hydrochloride. Drugs Fut 1986, 11, 8, 652. |
| 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) | 23143 | 1-Phenylacetone; Methyl benzyl ketone; Benzyl methyl ketone; phenylacetone; Phenyl-2-propanone | 103-79-7 | C9H10O | 详情 | 详情 |
| (II) | 24294 | 1-methyl-2-phenylethylamine | C9H13N | 详情 | 详情 | |
| (III) | 24295 | N-[2-(4-iodophenyl)-1-methylethyl]acetamide | C11H14INO | 详情 | 详情 | |
| (IV) | 24296 | 2-(4-Iodophenyl)-1-methylethylamine hydrochloride | C9H12IN | 详情 | 详情 | |
| (V) | 24297 | 1-(4-iodophenyl)-N-isopropyl-2-propanamine | C12H18IN | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)2) A route that does not involve controlled drugs (phenylacetone or amphetamine) proceeds from p-iodophenylacetic acid (VII). The starting material can be made in low yield by iodination of phenylacetic acid or by a two-step process from p-aminophenylacetic acid by diazotization and treatment with potassium iodide. Condensation of p-iodophenylacetic acid (VII) with acetic anhydride gives p-iodophenylacetone (VIII) in variable yields, depending on the purity of the starting carboxylic acid and en the choice of base. Reductive amination with isopropylamine then gives iofetamine (V) in good yield.
| 【1】 Stoermer, R.; Strioh, H.; Die Phenylbenzylbernsteinsaueren. Chem Ver 1935, 68, 2112. |
| 【2】 King, J.A.; Mc Millan, F.H.; The decarboxylate acylation of arylacetic acids. J Am Chem Soc 1951, 73, 6911, 4911. |
| 【3】 Lucas, H.J.; Kennedy, E.R.; Iodobenzene. Org Synth Coll 1943, II, 5, 351. |
| 【4】 Cavallini, G.; Massarani, E.; Nardi, D.; Applicazione dell reazione di Leukart ad alcuni fenil propan-2-oni sostituti in posizione para. Farm Sci Ed 1956, 11, 805. |
| 【5】 Andresen, K.; Carlsen, L.; 131I-labelled N-isopropyl-p-Iodoamphetamine. Eur J Nucl Med 1982, 7, 6, 280. |
| 【6】 Baldwin, R.M.; Iofetamine (123I) hydrochloride. Drugs Fut 1986, 11, 8, 652. |
合成路线3
该中间体在本合成路线中的序号：(V)3) A third sequence proceeds by condensation of p-iodobenzaldehyde (IX) with nitromethane, followed by reductive hydrolysis of the intermediate unsaturated nitrocompound, to yield p-iodophenylacetone (VIII). The final sequence is the same as in scheme 09034702a.
| 【1】 le Poncin-Lafitte, M.; Duterte, D.; Morier, E.; et al.; Synthesis of p-I-125 amphetamine. J Label Compd Radiopharm 1983, 20, 149. |
| 【2】 Coornaert, S.; Rapin, J.R.; Bardy, A.; et al.; New ways of obtaining N-isopropyl-p-iodoamphetamine and pharmacokinetic studies in rat. 3rd Wordl Cong Nucl Med Biol (Aug, Paris) 1982, 4, 23, 3598. |
| 【3】 Rapin, J.R.; et al.; Chemical and pharmacological aspects of cerebral cellular tracers. Ann Radiol 1983, 26, 1, 48. |
| 【4】 Baldwin, R.M.; Iofetamine (123I) hydrochloride. Drugs Fut 1986, 11, 8, 652. |