【结 构 式】 |
【药物名称】A-317920 【化学名称】N-[2-[4-[3-[4-(Cyclopropylcarbonyl)phenoxy]propyl]piperazin-1-yl]-1(R)-methyl-2-oxoethyl]furan-2-carboxamide 【CA登记号】360551-59-3 【 分 子 式 】C25H31N3O5 【 分 子 量 】453.54292 |
【开发单位】Abbott (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Histamine H3 Receptor Antagonists |
合成路线1
Intramolecular cyclization of p-hydroxy-4-chlorobutyrophenone (I) under alkaline conditions yields cyclopropyl(4-hydroxyphenyl) ketone (II). The phenolic hydroxyl group is then alkylated by 1-bromo-3-chloropropane (III) to furnish the chloropropyl ether (IV). Subsequent condensation of alkyl chloride (IV) with piperazine (V) gives rise to the N-substituted piperazine (VI). This is then coupled with N-Boc-L-alanine (VII) in the presence of EDC/DMAP to afford amide (VIII) (1, 2). After acidic cleavage of the N-Boc protecting group, the resultant monosubstituted piperazine (IX) is acylated by furanoyl chloride (X) to furnish the target furamide derivative
【1】 Black, L.A.; Faghih, R.; Liu, H.; et al.; Acyl-D-alanine amides: Selective histamine H3 receptor antagonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 323. |
【2】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. WO 0166534 . |
【3】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. US 2001049367; US 6559140 . |
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) | 62995 | C10H11ClO2 | 详情 | 详情 | ||
(II) | 27425 | cyclopropyl(4-hydroxyphenyl)methanone | C10H10O2 | 详情 | 详情 | |
(III) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
(IV) | 62988 | 5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine | C11H8BrN5 | 详情 | 详情 | |
(V) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
(VI) | 62996 | C17H24N2O2 | 详情 | 详情 | ||
(VII) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
(VIII) | 63042 | C28H23ClN2O2 | 详情 | 详情 | ||
(IX) | 63043 | C17H15ClN2O2 | 详情 | 详情 | ||
(X) | 26093 | 2-Furoyl chloride | 527-69-5 | C5H3ClO2 | 详情 | 详情 |