Medetomidine, MPV-785(hydrochloride), Domitor, -Drug Synthesis Database

【结构式】

【药物名称】Medetomidine, MPV-785(hydrochloride), Domitor

【化学名称】(±)-4-[1-(2,3-Dimethylphenyl)ethyl]imidazole

【CA登记号】86347-14-0, 86347-15-1 (HCl)

【分子式】C₁₃H₁₆N₂

【分子量】200.28587

【开发单位】Orion Corp. (Originator), Orion Pharma (Originator)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiglaucoma Agents, Anxiolytics, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Non-Opioid Analgesics, OCULAR MEDICATIONS, Ophthalmic Drugs, PSYCHOPHARMACOLOGIC DRUGS, Sedative/Hypnotics, Sleep Disorders, Treatment of

合成路线1 合成路线2

合成路线1

A new synthesis for medetomidine has been reported: The silylation of N,N-dimethylimidazole-1-sulfonamide (I) with tert-butyldimethylsilyl chloride and butyllithium in THF gives the 2-silyl derivative (II), which is acylated with 2,3-dimethylbenzoyl chloride (III) by means of butyllithium in THF, yielding 2-(tert-butyldimethylsilyl)-5-(2,3-dimethylbenzoyl)-N,N-dimethylimidazo le-1-sulfonamide (IV). Hydrolysis of (IV) with refluxing aqueous HCl affords 5-(2,3-dimethylbenzoyl)imidazole (V), which is finally methylated with methyllithium in THF and reduced with Li in liquid NH3.

参考文献中间体

【1】 Turnbull, S.P.; Kudzma, L.V.; Expedient synthesis of 4(5)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, the alpha2-adrenergic agonist medetomidine. Synthesis 1991, 11, 1201.

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)	11036	N,N-Dimethyl-1H-imidazole-1-sulfonamide	78162-58-0	C₅H₉N₃O₂S	详情	详情
(II)	11037	2-[tert-Butyl(dimethyl)silyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide		C₁₁H₂₃N₃O₂SSi	详情	详情
(III)	11038	2,3-Dimethylbenzoyl chloride	21900-46-9	C₉H₉ClO	详情	详情
(IV)	11039	2-[tert-Butyl(dimethyl)silyl]-5-(2,3-dimethylbenzoyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide		C₂₀H₃₁N₃O₃SSi	详情	详情
(V)	11040	(2,3-Dimethylphenyl)(1H-imidazol-4-yl)methanone		C₁₂H₁₂N₂O	详情	详情

合成路线2

The Grignard condensation of methyl imidazole-4-carboxyate (I) with 2,3-dimethylphenylmagnesium bromide (II) in THF gives 4-(2,3-dimethylbenzoyl) imidazole (III), which (without isolation) is submitted to a new Grignard condensation with methylmagnesium iodide (IV) in the same solvent to yield 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethanol (V). The dehydration of (V) with potassium hydrogen sulfate at 136 C affords 1-(4-imidazolyl)-1-(2,3-dimethyl-phenyl)ethylene (VI), which is finally hydrogenated with H2 over Pd/C in 2N HCl.

参考文献中间体

【1】 Hillier, K.; Acta Univ Oul 1981, 8, 4, A125.
【2】 Karjalainen, A.J.; Kurkela, K.O.A.; Pohjala, E.K. (Orion Pharma); Antihypertensive subtituted imidazole derivates. GB 2101114; US 4639464 .
【3】 Castaner, R.M.; Serradell, M.N.; Castaner, J.; Medetomidine. Drugs Fut 1987, 12, 11, 1021.

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)	27998	methyl 1H-imidazole-4-carboxylate	17325-26-7	C₅H₆N₂O₂	详情	详情
(II)	27999	bromo(2,3-dimethylphenyl)magnesium		C₈H₉BrMg	详情	详情
(III)	11040	(2,3-Dimethylphenyl)(1H-imidazol-4-yl)methanone		C₁₂H₁₂N₂O	详情	详情
(IV)	20225	iodo(methyl)magnesium	917-64-6	CH₃IMg	详情	详情
(V)	28000	1-(2,3-dimethylphenyl)-1-(1H-imidazol-4-yl)-1-ethanol		C₁₃H₁₆N₂O	详情	详情
(VI)	28001	4-[1-(2,3-dimethylphenyl)vinyl]-1H-imidazole		C₁₃H₁₄N₂	详情	详情

Extended Information