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【结 构 式】 
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【分子编号】50171 【品名】methyl 3-(bromomethyl)-2-phenyl-4-quinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C18H14BrNO2 【 分 子 量 】356.2187 【元素组成】C 60.69% H 3.96% Br 22.43% N 3.93% O 8.98% |
合成路线1
该中间体在本合成路线中的序号：(III)Esterification of the commercially available carboxylic acid (I) by treatment with oxalyl chloride in DCM followed by reaction with MeOH in CH2Cl2 provides methyl carboxylate (II), which is then brominated with NBS and catalytic dibenzoylperoxide in refluxing acetonitrile to afford 3-bromomethylquinoline derivative (III). Treatment of (III) with secondary amine (IV) and DIEA in THF furnishes compound (V), which is then converted into the desired product by acidic hydrolysis in refluxing HCl followed by coupling with primary amine (VI) by means of HBTU and Et3N in refluxing THF/CH2Cl2.
| 【1】 Blaney, F.E.; Artico, M.; Raveglia, L.F.; et al.; Stepwise modulation of neurokinin-3 and neurokinin-2 receptor affinity and selectivity in quinoline tachykinin receptor antagonists. J Med Chem 2001, 44, 11, 1675. |
| 【2】 Giardina, G.; Grugni, M.; Raveglia, L.F.; Nadler, G.M.M.G.; Farina, C. (SmithKline Beecham SpA); Quinoline derivs. as NK-2 and NK-3 receptor ligands. EP 1131294; WO 0031038 . |
| 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) | 50169 | 3-methyl-2-phenyl-4-quinolinecarboxylic acid | C17H13NO2 | 详情 | 详情 | |
| (II) | 50170 | methyl 3-methyl-2-phenyl-4-quinolinecarboxylate | C18H15NO2 | 详情 | 详情 | |
| (III) | 50171 | methyl 3-(bromomethyl)-2-phenyl-4-quinolinecarboxylate | C18H14BrNO2 | 详情 | 详情 | |
| (IV) | 10821 | 4-Piperidinopiperidine | 4897-50-1 | C10H20N2 | 详情 | 详情 |
| (V) | 50172 | C28H33N3O2 | 详情 | 详情 | ||
| (VI) | 30977 | (2R)-3,3-dimethyl-2-butanamine; (1R)-1,2,2-trimethylpropylamine | C6H15N | 详情 | 详情 |