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【结 构 式】 
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【分子编号】57018 【品名】ethyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate 【CA登记号】 |
【 分 子 式 】C13H16ClNO6 【 分 子 量 】317.72588 【元素组成】C 49.14% H 5.08% Cl 11.16% N 4.41% O 30.21% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of 4-hydroxy-3-methoxybenzoic acid ethyl ester (I) with 3-chloropropyl bromide (II) by means of K2CO3 in refluxing DMF gives the 4(3-chloropropoxy)-3-methoxybenzoic acid ethyl ester (III), which is nitrated by means of HNO3 and AcOH to yield the 2-nitro derivative (IV). The condensation of (IV) with piperidine (V) by means of K2CO3 in hot toluene affords 5-methoxy-2-nitro-4-[3-(1-piperidinyl)propoxy]benzoic acid ethyl ester (VI), which is reduced by means of Pd/C and HCO2K in ethanol/water to provide the 2-amino derivative (VII). The cyclization of (VII) with formamide and ammonium formate at 135 C gives the quinazoline (VIII), which is treated with SOCl2 in refluxing toluene to yield the chloro derivative (IX). Finally this compound is condensed with the piperazinecarboxamide (X) by means of K2CO3 in hot DMF/toluene to afford the target CT-53518.
| 【1】 Pandey, A.; et al.; Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family. J Med Chem 2002, 45, 17, 3772. |
| 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) | 57016 | 3-Methoxy-4-hydroxybenzoic acid ethyl ester; 4-Hydroxy-3-methoxybenzoic acid ethyl ester; Ethyl 4-hydroxy-3-methoxybenzoate; Ethyl vanillate; Ethyl-3-Methoxy-4-Hydroxybenzoate; Vanillic acid ethyl ester | 617-05-0 | C10H12O4 | 详情 | 详情 |
| (II) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (III) | 57017 | ethyl 4-(3-chloropropoxy)-3-methoxybenzoate | C13H17ClO4 | 详情 | 详情 | |
| (IV) | 57018 | ethyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate | C13H16ClNO6 | 详情 | 详情 | |
| (V) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (VI) | 57019 | ethyl 5-methoxy-2-nitro-4-[3-(1-piperidinyl)propoxy]benzoate | C18H26N2O6 | 详情 | 详情 | |
| (VII) | 57020 | ethyl 2-amino-5-methoxy-4-[3-(1-piperidinyl)propoxy]benzoate | C18H28N2O4 | 详情 | 详情 | |
| (VIII) | 57021 | 6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinol | C17H23N3O3 | 详情 | 详情 | |
| (IX) | 57022 | 4-chloro-6-methoxy-7-[3-(1-piperidinyl)propoxy]quinazoline; 4-chloro-6-methoxy-7-quinazolinyl 3-(1-piperidinyl)propyl ether | C17H22ClN3O2 | 详情 | 详情 | |
| (X) | 57023 | N-(4-isopropoxyphenyl)-1-piperazinecarboxamide | C14H21N3O2 | 详情 | 详情 |