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【结 构 式】 
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【分子编号】43063 【品名】3-bromo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid 【CA登记号】 |
【 分 子 式 】C13H9BrN2O3 【 分 子 量 】321.13014 【元素组成】C 48.62% H 2.82% Br 24.88% N 8.72% O 14.95% |
合成路线1
该中间体在本合成路线中的序号：(V)Treatment of 4-bromophthalic anhydride (I) in MeOH with NaOMe affords methyl ester (II), which is then treated with diphenylphosphoryl azide ((PhO)2PON3) in toluene, acetone/H2O to yield a mixture of regioisomers from which derivative (III) is obtained by chromatographic separation. Condensation of (III) with 2-chloronicotinic acid (IV) in refluxing EtOH in the presence of HCl yields pyridoquinazoline acid derivative (V), which is then condensed with N,N-dimethylethylenediamine (VI) in CH2Cl2 using BOP as coupling reagent to provide (VII). Reaction of 2-bromopyridine (VIII) in Et2O with n-BuLi and trimethylborate, followed by treatment with EtOH and HOAc, gives 3-pyridinyl boronic acid (IX), which is finally coupled to (VII) 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) | 43060 | 5-bromo-2-benzofuran-1,3-dione | 86-90-8 | C8H3BrO3 | 详情 | 详情 |
| (II) | 43061 | 5-bromo-2-(methoxycarbonyl)benzoic acid | C9H7BrO4 | 详情 | 详情 | |
| (III) | 43062 | methyl 2-amino-4-bromobenzoate | 135484-83-2 | C8H8BrNO2 | 详情 | 详情 |
| (IV) | 28824 | 2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid | 2942-59-8 | C6H4ClNO2 | 详情 | 详情 |
| (V) | 43063 | 3-bromo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid | C13H9BrN2O3 | 详情 | 详情 | |
| (VI) | 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 |
| (VII) | 43064 | 3-bromo-N-[2-(dimethylamino)ethyl]-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxamide | C17H19BrN4O2 | 详情 | 详情 | |
| (VIII) | 13265 | 3-Bromopyridine | 626-55-1 | C5H4BrN | 详情 | 详情 |
| (IX) | 38825 | 3-pyridinylboronic acid | 1692-25-7 | C5H6BNO2 | 详情 | 详情 |