【结 构 式】 |
【药物名称】A-349821 【化学名称】1-[4'-[3-[2(R),5(R)-Dimethylpyrrolidin-1-yl]propoxy]biphenyl-4-yl]-1-(4-morpholinyl)methanone 【CA登记号】372513-99-0 【 分 子 式 】C26H34N2O3 【 分 子 量 】422.57248 |
【开发单位】Abbott (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Antiepileptic Drugs, Antipsychotic Drugs, Attention Deficit Hyperactivity Disorder (ADHD), Treatment of, Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Histamine H3 Receptor Antagonists |
合成路线1
Fischer esterification of 4'-hydroxybiphenyl-4-carboxylic acid (I) with H2SO4/MeOH provides ester (II). The phenolic hydroxyl group is then alkylated with 1-bromo-3-chloropropane (III) in the presence of K2CO3 to furnish the chloropropyl ether (IV). Saponification of methyl ester (IV) with LiOH leads to carboxylic acid (V), which is further activated as the corresponding acid chloride (VI) upon heating in SOCl2. Acid chloride (VI) is subsequently coupled with morpholine (VII) to yield amide (VIII). Finally, alkyl chloride (VIII) is displaced with (R,R)-2,5-dimethylpyrrolidine (IX) in the presence of K2CO3 and KI to furnish the title compound.
【1】 Faghih, R.; Bennani, Y.L. (Abbott Laboratories Inc.); Aminoalkoxybiphenyl carboxamides as histamine-3 receptor ligands and their therapeutic applications. US 6316475; WO 0240461 . |
【2】 Faghih, R.; Bennani, Y.; Aminoalkoxybiphenylcarboxamides as histamine-3 receptor ligands and their therapeutic applications. US 2002111340 . |
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) | 63280 | 4'-hydroxy[1,1'-biphenyl]-4-carboxylic acid | C13H10O3 | 详情 | 详情 | |
(II) | 63281 | methyl 4'-hydroxy[1,1'-biphenyl]-4-carboxylate | C14H12O3 | 详情 | 详情 | |
(III) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
(IV) | 63282 | methyl 4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carboxylate | C17H17ClO3 | 详情 | 详情 | |
(V) | 63283 | 4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carboxylic acid | C16H15ClO3 | 详情 | 详情 | |
(VI) | 63284 | 4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carbonyl chloride | C16H14Cl2O2 | 详情 | 详情 | |
(VII) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
(VIII) | 63285 | [4'-(3-chloropropoxy)[1,1'-biphenyl]-4-yl](4-morpholinyl)methanone | C20H22ClNO3 | 详情 | 详情 | |
(IX) | 63286 | (2R,5R)-2,5-dimethylpyrrolidine | C6H13N | 详情 | 详情 |