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【结 构 式】

【分子编号】14566

【品名】methyl 4-[(2-butyl-5-formyl-4-iodo-1H-imidazol-1-yl)methyl]benzoate

【CA登记号】

【 分 子 式 】C17H19IN2O3

【 分 子 量 】426.25401

【元素组成】C 47.9% H 4.49% I 29.77% N 6.57% O 11.26%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

Eprosartan has been obtained by several different ways: 1) The iodination of 2-butylimidazole (I) with I2 and Na2CO3 in dioxane/water gives 2-butyl-4,5-diiodoimidazole (II), which is treated with benzyl chloromethyl ether (III) and K2CO3 in DMF yielding the imidazole derivative (IV). The condensation of (IV) with N-methyl-N-(2-pyridyl)formamide (V) by means of butyllithium in THF affords 1-(benzyloxymethyl)-2-butyl-4-iodoimidazole-5-carbaldehyde (VI), which is deprotected with concentrated HCl ethanol to give 2-butyl-4-iodoimidazole-5-carbaldehyde (VII). The acylation of (VII) with methyl 4-(bromomethyl)benzoate (VIII) by means of K2CO3 in hot DMF yields 4-(2-butyl-5-formyl-4-iodoimidazol-1 ylmethyl)benzoic acid methyl ester (IX), which is deiodinated by hydrogenation with H2 over Pd/C in methanol affording compound (X). The condensation of (X) with methyl 3-(2-thienyl)propionate (XI) by means of lithium diisopropylamide (LDA) in THF gives (XII), which is acylated with acetic anhydride and dimethylaminopyridine (DMAP) in dichloromethane yielding the corresponding acetate (XIII). Elimination of acetic acid from (XIII) with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in hot toluene affords the expected propenoic ester (XIV), which is finally saponified with NaOH or KOH in ethanol/water.

1 Wittenberger, S.J.; Tasker, A.; Sorensen, B.K.; Donner, B.G.; 2-Butyl-4-iodoimidazole-5-carboxaldehyde: A versatile intermediate for the synthesis of highly functionalized imidazoles. Synth Commun 1993, 23, 22, 3231-48.
2 Merlos, M.; Casas, A.; Graul, A.; Castaner, J.; Eprosartan. Drugs Fut 1997, 22, 10, 1079.
3 Keenan, R.M.; Weinstock, J.; Finkelstein, J.A.; et al.; Potent nonpeptide angiotensin II receptor antagonists. 2. 1-(Carboxybenzyl)imidazole-5-acrylic acids. J Med Chem 1993, 36, 13, 1880-92.
4 Weinstock, J.; Keenan, R.M.; Samanen, J.; et al.; 1-(Carboxybenzyl)imidazole-5-acrylic acids: Potent and selective angiotensin II receptor antagonists. J Med Chem 1991, 34, 4, 1514-7.
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) 14558 2-butyl-1H-imidazole 50790-93-7 C7H12N2 详情 详情
(II) 14559 2-butyl-4,5-diiodo-1H-imidazole C7H10I2N2 详情 详情
(III) 14560 Benzyl chloromethyl ether; 1-[(chloromethoxy)methyl]benzene 3587-60-8 C8H9ClO 详情 详情
(IV) 14561 1-[(benzyloxy)methyl]-2-butyl-4,5-diiodo-1H-imidazole; benzyl (2-butyl-4,5-diiodo-1H-imidazol-1-yl)methyl ether C15H18I2N2O 详情 详情
(V) 14562 N-Methyl-n-(2-pyridyl)formamide; N-methyl-N-(2-pyridinyl)formamide 67242-59-5 C7H8N2O 详情 详情
(VI) 14563 1-[(benzyloxy)methyl]-2-butyl-4-iodo-1H-imidazole-5-carbaldehyde C16H19IN2O2 详情 详情
(VII) 14564 2-butyl-4-iodo-1H-imidazole-5-carbaldehyde C8H11IN2O 详情 详情
(VIII) 14565 methyl 4-(bromomethyl)benzoate 2417-72-3 C9H9BrO2 详情 详情
(IX) 14566 methyl 4-[(2-butyl-5-formyl-4-iodo-1H-imidazol-1-yl)methyl]benzoate C17H19IN2O3 详情 详情
(X) 14567 methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoate C17H20N2O3 详情 详情
(XI) 14568 methyl 3-(2-thienyl)propanoate 16862-05-8 C8H10O2S 详情 详情
(XII) 14569 methyl 4-([2-butyl-5-[1-hydroxy-3-methoxy-3-oxo-2-(2-thienylmethyl)propyl]-1H-imidazol-1-yl]methyl)benzoate C25H30N2O5S 详情 详情
(XIII) 14570 methyl 4-([5-[1-(acetoxy)-3-methoxy-3-oxo-2-(2-thienylmethyl)propyl]-2-butyl-1H-imidazol-1-yl]methyl)benzoate C27H32N2O6S 详情 详情
(XIV) 14571 methyl 4-([2-butyl-5-[(E)-3-methoxy-3-oxo-2-(2-thienylmethyl)-1-propenyl]-1H-imidazol-1-yl]methyl)benzoate C25H28N2O4S 详情 详情
Extended Information