【结 构 式】 |
【药物名称】CK-0106023 【化学名称】N-[1-(3-Benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)propyl]-4-bromo-N-[3-(dimethylamino)propyl]benzamide 【CA登记号】336115-72-1 【 分 子 式 】C30H32BrClN4O2 【 分 子 量 】595.97214 |
【开发单位】Cytokinetics (Originator), GlaxoSmithKline (Codevelopment) 【药理作用】ONCOLYTIC DRUGS, Antimitotic Drugs, Kinesin-Like Spindle Protein (Eg5) Inhibitors |
合成路线1
4-Chloroanthranilic acid (I) is acylated by butyryl chloride (II) in DMF to produce amide (III). This is then cyclized to the benzoxazinone (IV) upon heating with acetic anhydride. Condensation of (IV) with benzylamine (V) in refluxing chloroform, followed by treatment with NaOH in hot ethyleneglycol, gives rise to the quinazolinone (VI). Subsequent benzylic bromination of (VI) at the propyl side chain produces (VII). The bromide group of (VII) is then displaced with N,N-dimethyl-1,3-propanediamine (VIII) to furnish (IX). Finally, amine (IX) is acylated by 4-bromobenzoyl chloride (X) to afford the corresponding benzamide.
【1】 Chabala, J.C.; Morgans, D.J. Jr.; Feng, B.; Finer, J.T.; Bergnes, G.; Smith, W.W. (Cytokinetics, Inc.); Methods and compsns. utilizing quinazolinones. WO 0198278 . |
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) | 52504 | 4-Chloro-2-aminobenzoic acid; 2-Amino-4-chlorobenzoic acid; 2-Carboxy-5-chloroaniline; 3-Amino-4-carboxy-1-chlorobenzene; 4-Chloroanthranilic acid | 89-77-0 | C7H6ClNO2 | 详情 | 详情 |
(II) | 10792 | Butanoyl chloride; Butyryl chloride | 141-75-3 | C4H7ClO | 详情 | 详情 |
(III) | 58445 | 2-(butyrylamino)-4-chlorobenzoic acid | C11H12ClNO3 | 详情 | 详情 | |
(IV) | 58446 | 7-chloro-2-propyl-4H-3,1-benzoxazin-4-one | C11H10ClNO2 | 详情 | 详情 | |
(V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
(VI) | 58447 | 3-benzyl-7-chloro-2-propyl-4(3H)-quinazolinone | C18H17ClN2O | 详情 | 详情 | |
(VII) | 58448 | 3-benzyl-2-(1-bromopropyl)-7-chloro-4(3H)-quinazolinone | C18H16BrClN2O | 详情 | 详情 | |
(VIII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
(IX) | 58449 | 3-benzyl-7-chloro-2-(1-{[3-(dimethylamino)propyl]amino}propyl)-4(3H)-quinazolinone | C23H29ClN4O | 详情 | 详情 | |
(X) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |