【结 构 式】 |
【药物名称】FAUC-179 【化学名称】1-Phenyl-4-[2-phenyl-4,5-dihydro-1H-imidazol-4(R)-ylmethyl]piperazine hydrochloride 【CA登记号】 【 分 子 式 】C20H25ClN4 【 分 子 量 】356.90205 |
【开发单位】Friedrich-Alexander-Universität (Originator) 【药理作用】Attention Deficit Hyperactivity Disorder (ADHD), Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Dopamine D4 Partial Agonists |
合成路线1
Cyclization of (R)-serine methyl ester (I) with methyl benzimidate (II) gave oxazolidine (III). Reduction of the methyl ester function of (III) with LiAlH4 at low temperature afforded the hydroxymethyl derivative (IV), which was further activated as the mesylate (V). Displacement of the mesylate group of (V) with phenylpiperazine (VI) resulted in the formation of the disubstituted piperazine (VII). Nucleophilic ring opening of oxazolidine (VII) by azidotrimethylsilane yielded azide (VIII). Both the amide and azide functions of (VIII) were subsequently reduced with LiAlH4 to produce (IX). Hydrogenolysis of the benzyl amine (IX) over Pearlman's catalyst furnished the chiral ethylenediamine (X). The title imidazoline was finally obtained by cyclization of diamine (X) with methyl benzimidate (II) as its hydrochloride form in refluxing MeOH.
【1】 Einsiedel, J.; et al.; Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179). Bioorg Med Chem Lett 2001, 11, 18, 2533. |
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) | 21813 | methyl (2R)-2-amino-3-hydroxypropanoate | C4H9NO3 | 详情 | 详情 | |
(II) | 52039 | methyl benzenecarboximidoate | C8H9NO | 详情 | 详情 | |
(III) | 52040 | methyl (4R)-2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxylate | C11H11NO3 | 详情 | 详情 | |
(IV) | 52041 | [(4S)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methanol | C10H11NO2 | 详情 | 详情 | |
(V) | 52042 | [(4R)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methyl methanesulfonate | C11H13NO4S | 详情 | 详情 | |
(VI) | 10756 | N-Phenylpiperazine; 1-Phenylpiperazine; Phenyl piperazine | 92-54-6 | C10H14N2 | 详情 | 详情 |
(VII) | 52043 | 1-phenyl-4-[[(4S)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methyl]piperazine | C20H23N3O | 详情 | 详情 | |
(VIII) | 52044 | N-[(1S)-2-azido-1-[(4-phenyl-1-piperazinyl)methyl]ethyl]benzamide | C20H24N6O | 详情 | 详情 | |
(IX) | 52045 | N-[(1R)-2-amino-1-[(4-phenyl-1-piperazinyl)methyl]ethyl]-N-benzylamine; (2R)-N(2)-benzyl-3-(4-phenyl-1-piperazinyl)-1,2-propanediamine | C20H28N4 | 详情 | 详情 | |
(X) | 52046 | (2R)-3-(4-phenyl-1-piperazinyl)-1,2-propanediamine; (1R)-2-amino-1-[(4-phenyl-1-piperazinyl)methyl]ethylamine | C13H22N4 | 详情 | 详情 |