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【结 构 式】 
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【分子编号】24298 【品名】2-(4-iodophenyl)acetic acid 【CA登记号】1798-06-7 |
【 分 子 式 】C8H7IO2 【 分 子 量 】262.04685 【元素组成】C 36.67% H 2.69% I 48.43% O 12.21% |
合成路线1
该中间体在本合成路线中的序号：(VII)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2
该中间体在本合成路线中的序号：(X)The cyclization of 3-hydroxy-1,2-phenylenediamine (I) with 2-phenoxyacetonitrile (II) by means of sodium methoxide in methanol gives the benzimidazole (III), which is acylated with 4-(3-bromopropyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH and KI in hot DMF yielding the N-alkylated benzimidazole (V). The alkylation of the hydroxy group of (V) with 1-(3-bromopropyl)piperidine (VI) by means of NaH and KI as before affords the dialkylated benzimidazole (VII), which is deprotected with TFA in dichloromethane affording the free piperidine (VIII). Finally, the piperidine group of (VIII) is alkylated with 2-(4-iodophenyl)ethyl bromide (IX) by means of NaHCO3 in hot DMF.
| 【1】 Cantrell, B.E.; Zarrinmayeh, H.; Zimmerman, D.M.; et al.; Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists. Bioorg Med Chem Lett 1999, 9, 5, 647. |
| 【2】 Nunes, A.M.; Zarrinmayeh, H.; Ornstein, P.L.; et al.; Synthesis and evaluation of a series of novel 2-[(4-chlorophenoxy)methyl]benzimidazoles as selective neuropeptide Y Y1 receptor antagonists. J Med Chem 1998, 41, 15, 2709. |
| 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) | 30964 | 2,3-diaminophenol | C6H8N2O | 详情 | 详情 | |
| (II) | 30965 | 2-phenoxyacetonitrile | 3598-14-9 | C8H7NO | 详情 | 详情 |
| (III) | 30966 | 2-(phenoxymethyl)-1H-benzimidazol-4-ol | C14H12N2O2 | 详情 | 详情 | |
| (IV) | 30967 | tert-butyl 4-(3-bromopropyl)-1-piperidinecarboxylate | C13H24BrNO2 | 详情 | 详情 | |
| (V) | 30968 | tert-butyl 4-[3-[4-hydroxy-2-(phenoxymethyl)-1H-benzimidazol-1-yl]propyl]-1-piperidinecarboxylate | C27H35N3O4 | 详情 | 详情 | |
| (VI) | 30969 | 1-(3-bromopropyl)piperidine | C8H16BrN | 详情 | 详情 | |
| (VII) | 30970 | tert-butyl 4-(3-[2-(phenoxymethyl)-4-[3-(1-piperidinyl)propoxy]-1H-benzimidazol-1-yl]propyl)-1-piperidinecarboxylate | C35H50N4O4 | 详情 | 详情 | |
| (VIII) | 30971 | 2-(phenoxymethyl)-1-[3-(4-piperidinyl)propyl]-1H-benzimidazol-4-yl 3-(1-piperidinyl)propyl ether; 2-(phenoxymethyl)-4-[3-(1-piperidinyl)propoxy]-1-[3-(4-piperidinyl)propyl]-1H-benzimidazole | C30H42N4O2 | 详情 | 详情 | |
| (IX) | 30972 | 1-(2-bromoethyl)-4-iodobenzene | C8H8BrI | 详情 | 详情 | |
| (X) | 24298 | 2-(4-iodophenyl)acetic acid | 1798-06-7 | C8H7IO2 | 详情 | 详情 |
| (XI) | 30973 | 2-(4-iodophenyl)-1-ethanol | C8H9IO | 详情 | 详情 |