2-Butyl-5-hydroxymethylimidazole; (2-Butyl-1H-imidazol-5-yl)methanol -Drug Synthesis Database

【结构式】

【分子编号】13923

【品名】2-Butyl-5-hydroxymethylimidazole; (2-Butyl-1H-imidazol-5-yl)methanol

【CA登记号】68283-19-2

【分子式】C₈H₁₄N₂O

【分子量】154.21204

【元素组成】C 62.31% H 9.15% N 18.17% O 10.37%

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：(III)

Synthesis of imidazole (V) first entails the conversion of valeronitrile (I) to its imidate ester (II). Subsequent reaction with 1,3-dihydroxyacetone dimer and ammonia leads to imidazole (III). Chlorination with N-chlorosuccinimide yields the 4-chloroimidazole (IV). Oxidation with manganese dioxide finally yields imidazole-5-carboxaldehyde (V).

参考文献中间体

合成目标

【1】 Carini, D.J.; Duncia, J.V.; Aldrich, P.E.; Chiu, A.T.; Johnson, A.L.; Pierce, M.E.; Santella, J.B.; Wells, G.J.; Wexler, R.R.; Wong, P.C.; Timmermans, P.B.M.W.M.; Nonpeptide angiotensin II receptor antagonists: The discovery of a series of N-(biphenylmethyl)imidazoles as potent, orally-active antihypertensives. J Med Chem 1991, 34, 8, 2225-47.
【2】 Duncia, J.V.; Carini, D.J.; Chiu, A.T.; Pierce, M.E.; Price, W.A.; Smith, R.D.; Wells, G.J.; Wong, P.C.; Wexler, R.R.; Johnson, A.L.; Timmermans, P.B.M.W.M.; DuP 753. Drugs Fut 1991, 16, 4, 305.

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)	13921	Pentanenitrile; n-Valeronitrile	110-59-8	C₅H₉N	详情	详情
(II)	13922	Methyl pentanimidoate hydrocloride		C₆H₁₄ClNO	详情	详情
(III)	13923	2-Butyl-5-hydroxymethylimidazole; (2-Butyl-1H-imidazol-5-yl)methanol	68283-19-2	C₈H₁₄N₂O	详情	详情
(IV)	13924	2-Butyl-4-chloro-5-(hydroxymethyl)imidazole; (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol	79047-41-9	C₈H₁₃ClN₂O	详情	详情
(V)	13925	2-Butyl-4-chloro-1H-imidazole-5-carbaldehyde	83857-96-9	C₈H₁₁ClN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVII)

3) The cyclization of 1,3-dihydroxyacetone (XV) with pentanamidine (XVI) in liquid ammonia gives 2-butyl-5-(hydroxymethyl)imidazole (XVII), which is acetylated with acetic anhydride yielding 5 (acetoxymethyl)-1-acetyl-2-butylimidazole (XVIII). The condensation of (XVIII) with methyl 4-(hydroxymethyl)benzoate (XIX) by means of trifluoroacetic anhydride and diisopropylethylamine in dichloromethane affords 4-[5-(acetoxymethyl)-2-butylimidazol-1-ylmethyl)benzoic acid methyl ester (XX), which is hydrolyzed with NaOH in methanol/water giving 4-[2-butyl-5-(hydroxymethyl)imidazol-1-ylmethyl)benzoic acid (XXI). The controlled oxidation of (XXI) with activated MnO2 in toluene/dichloromethane yields the corresponding aldehyde (XXII), which is condensed with methyl 3-(2-thienyl)propionate (XI) with LDA in THF affording (XXIII). The acetylation of (XXIII) with acetic anhydride and DMAP gives the corresponding acetate (XXIV), which is treated with DBU as before yielding the propenoate (XXV). Finally, this compound is hydrolyzed with NaOH as already described.

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】 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.
【4】 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.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	14568	methyl 3-(2-thienyl)propanoate	16862-05-8	C₈H₁₀O₂S	详情	详情
(XV)	14575	Dihydroxyacetone; 1,3-dihydroxyacetone	96-26-4	C₃H₆O₃	详情	详情
(XVI)	14576	pentanimidamide	109-51-3	C₅H₁₂N₂	详情	详情
(XVII)	13923	2-Butyl-5-hydroxymethylimidazole; (2-Butyl-1H-imidazol-5-yl)methanol	68283-19-2	C₈H₁₄N₂O	详情	详情
(XVIII)	14578	(1-acetyl-2-butyl-1H-imidazol-5-yl)methyl acetate	136701-34-3	C₁₂H₁₈N₂O₃	详情	详情
(XIX)	14579	methyl 4-(hydroxymethyl)benzoate; Methyl 4-hydroxymethylbenzoate	6908-41-4	C₉H₁₀O₃	详情	详情
(XX)	14580	methyl 4-([5-[(acetoxy)methyl]-2-butyl-1H-imidazol-1-yl]methyl)benzoate		C₁₉H₂₄N₂O₄	详情	详情
(XXI)	14581	4-[[2-butyl-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]benzoic acid		C₁₆H₂₀N₂O₃	详情	详情
(XXII)	14582	4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid		C₁₆H₁₈N₂O₃	详情	详情
(XXIII)	14583	4-([2-butyl-5-[1-hydroxy-3-methoxy-3-oxo-2-(2-thienylmethyl)propyl]-1H-imidazol-1-yl]methyl)benzoic acid		C₂₄H₂₈N₂O₅S	详情	详情
(XXIV)	14584	4-([5-[1-(acetoxy)-3-methoxy-3-oxo-2-(2-thienylmethyl)propyl]-2-butyl-1H-imidazol-1-yl]methyl)benzoic acid		C₂₆H₃₀N₂O₆S	详情	详情
(XXV)	14585	4-([2-butyl-5-[(E)-3-methoxy-3-oxo-2-(2-thienylmethyl)-1-propenyl]-1H-imidazol-1-yl]methyl)benzoic acid		C₂₄H₂₆N₂O₄S	详情	详情

Extended Information