【结 构 式】 |
【药物名称】 【化学名称】N-[2-(Dimethylamino)ethyl)-11-oxo-2-(3-pyridyl)-11H-pyrido[2,1-b]quinazoline-6-carboxamide 【CA登记号】 【 分 子 式 】C22H21N5O2 【 分 子 量 】387.44497 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Oncolytic Drugs, DNA Topoisomerase II Inhibitors |
合成路线1
Condensation of 2-amino-4-iodobenzoic acid (I) with 2-chloronicotinic acid (II) in refluxing EtOH in the presence of HCl yields pyridoquinazoline acid derivative (III), which is then condensed with N,N-dimethylethylenediamine (IV) in CH2Cl2 using BOP as coupling reagent to provide (V). Reaction of 2-bromopyridine (VI) in Et2O with n-BuLi and trimethylborate, followed by treatment with EtOH and HOAc, gives 3-pyridinyl boronic acid (VII), which is finally coupled to (V) in an Na2CO3 solution via a Suzuki coupling catalyzed by Pd(PPh3)4.
【1】 Kitchen, D.B.; Schow, S.R.; Casscles, W.T. Jr.; Discafani, C.; Trova, M.P.; Lassota, P.; Zhang, N.; Powell, D.W.; Hetero biarylpyridoquinazolinone derivatives as anticancer agents. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 59. |
【2】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. EP 0944628; WO 9823617 . |
【3】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. US 5908840 . |
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) | 19964 | 5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid | 5326-47-6 | C7H6INO2 | 详情 | 详情 |
(II) | 28824 | 2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid | 2942-59-8 | C6H4ClNO2 | 详情 | 详情 |
(III) | 42991 | 2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid | C13H9IN2O3 | 详情 | 详情 | |
(IV) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
(V) | 42992 | N-[2-(dimethylamino)ethyl]-2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxamide | C17H19IN4O2 | 详情 | 详情 | |
(VI) | 13265 | 3-Bromopyridine | 626-55-1 | C5H4BrN | 详情 | 详情 |
(VII) | 38825 | 3-pyridinylboronic acid | 1692-25-7 | C5H6BNO2 | 详情 | 详情 |