3-methoxy-3-oxo-2-(2-thienylmethyl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】14574

【品名】3-methoxy-3-oxo-2-(2-thienylmethyl)propionic acid

【CA登记号】

【分子式】C₉H₁₀O₄S

【分子量】214.242

【元素组成】C 50.46% H 4.7% O 29.87% S 14.97%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVII)

2) The condensation of 2-butyl-4-chloroimidazole-5-carbaldehyde (XV) with methyl 4-(bromomethyl)benzoate (VIII) by means of K2CO3 in DMF yields 4-(2-butyl-4-chloro-5-formylimidazol-1-ylmethyl)benzoic acid methyl ester (XVI), which is dechlorinated by hydrogenation with H2 over Pd/C in methanol affording compound (X). The condensation of (X) with 2-(2-thienylmethyl)malonic acid monomethyl ester (XVII) by means of piperidine/pyridine in toluene gives the previously described compound (XIV), which is finally saponified with KOH in ethanol.

参考文献中间体

合成目标

【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
(VIII)	14565	methyl 4-(bromomethyl)benzoate	2417-72-3	C₉H₉BrO₂	详情	详情
(X)	14567	methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoate		C₁₇H₂₀N₂O₃	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
(XV)	13925	2-Butyl-4-chloro-1H-imidazole-5-carbaldehyde	83857-96-9	C₈H₁₁ClN₂O	详情	详情
(XVI)	14573	methyl 4-[(2-butyl-4-chloro-5-formyl-1H-imidazol-1-yl)methyl]benzoate		C₁₇H₁₉ClN₂O₃	详情	详情
(XVII)	14574	3-methoxy-3-oxo-2-(2-thienylmethyl)propionic acid		C₉H₁₀O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Ethylenediamine (I) was selectively monoprotected as the N-Boc derivative (II) and then coupled with sulfonyl chloride (III), yielding sulfonamide (IV). After deprotection of the Boc group of (IV) with HCl in dioxan, the resulting amine (V) was condensed with hydroxyacid (VI) by means of BOP reagent to give amide (VII). Acid deprotection of the Boc group of (VII), followed by condensation with 2,6-dichlorobenzoyl chloride (IX), provided (X). Finally, the hydroxyl group of (X) was oxidized to the title ketone employing the Dess-Martin periodinane reagent in CH2Cl2.

参考文献中间体

合成目标

【1】 Ator, M.A.; Mallamo, J.P.; Chatterjee, S.; Tao, M.; Wells, G.; Dunn, D.; Bihovsky, R.; Siman, R.; Gu, Z.-Q; P2-Achiral, P'-extended alpha-ketoamide inhibitors of calpain I. Bioorg Med Chem Lett 1999, 9, 16, 2371.
【2】 Wells, G.J.; Mallamo, J.P.; Chatterjee, S.; Bihovsky, R. (Cephalon, Inc.); Peptidyl-containing alpha-ketoamide cysteine and serine protease inhibitors. US 6150378 .

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)	14574	3-methoxy-3-oxo-2-(2-thienylmethyl)propionic acid		C₉H₁₀O₄S	详情	详情
(II)	13241	N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate	57260-73-8	C₇H₁₆N₂O₂	详情	详情
(III)	43065	5-(3-cyanophenyl)-2-thiophenesulfonyl chloride		C₁₁H₆ClNO₂S₂	详情	详情
(IV)	43066	tert-butyl 2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethylcarbamate		C₁₈H₂₁N₃O₄S₂	详情	详情
(V)	43067	N-(2-aminoethyl)-5-(3-cyanophenyl)-2-thiophenesulfonamide		C₁₃H₁₃N₃O₂S₂	详情	详情
(VI)	43071	(3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyric acid		C₁₅H₂₁NO₅	详情	详情
(VII)	43068	tert-butyl (1S)-1-benzyl-3-[[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]amino]-2-hydroxy-3-oxopropylcarbamate		C₂₈H₃₂N₄O₆S₂	详情	详情
(VIII)	43069	(3S)-3-amino-N-[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]-2-hydroxy-4-phenylbutanamide		C₂₃H₂₄N₄O₄S₂	详情	详情
(IX)	25087	2,6-dichlorobenzoyl chloride	4659-45-4	C₇H₃Cl₃O	详情	详情
(X)	43070	N-((1S)-1-benzyl-3-[[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]amino]-2-hydroxy-3-oxopropyl)-2,6-dichlorobenzamide		C₃₀H₂₆Cl₂N₄O₅S₂	详情	详情

Extended Information