2-Butyl-4-chloro-5-(hydroxymethyl)imidazole; (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol -Drug Synthesis Database

【结构式】

【分子编号】13924

【品名】2-Butyl-4-chloro-5-(hydroxymethyl)imidazole; (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol

【CA登记号】79047-41-9

【分子式】C₈H₁₃ClN₂O

【分子量】188.6568

【元素组成】C 50.93% H 6.95% Cl 18.79% N 14.85% O 8.48%

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：(IV)

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：(VII)

The methylation of 2-(2,6-difluorophenyl)acetic acid (I) with Me-Cl and LDA in THF/HMPA gives 2-(2,6-difluorophenyl)propionic acid (II), which is condensed with 2-methylmalonic acid monoethyl ester potassium salt (III) to yield 4-(2,6-difluorophenyl)-2-methyl-3-oxopentanoic acid (IV). The cyclization of (IV) with thiourea (V) affords 6-[1-(2,6-difluorophenyl)ethyl]-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (VI), which is finally alkylated with isobutyl chloride (VII) to provide the target pyrimidinone derivative.

参考文献中间体

合成目标

【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.

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)	51809	2,6-Difluorophenylacetic acid	85068-28-6	C₈H₆F₂O₂	详情	详情
(II)	51820	2-(2,6-difluorophenyl)propionic acid		C₉H₈F₂O₂	详情	详情
(III)	51813	potassium 3-ethoxy-2-methyl-3-oxopropanoate		C₆H₉KO₄	详情	详情
(IV)	51821	ethyl 4-(2,6-difluorophenyl)-2-methyl-3-oxopentanoate		C₁₄H₁₆F₂O₃	详情	详情
(V)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VI)	51822	6-[1-(2,6-difluorophenyl)ethyl]-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₃H₁₂F₂N₂OS	详情	详情
(VII)	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

Extended Information