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【结 构 式】

【分子编号】18297

【品名】4-(chloromethyl)-2-fluoropyridine

【CA登记号】

【 分 子 式 】C6H5ClFN

【 分 子 量 】145.5635432

【元素组成】C 49.51% H 3.46% Cl 24.36% F 13.05% N 9.62%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

Chlorination of 2-fluoro-4-picoline (I) with N-chlorosuccinimide in the presence of benzoyl peroxide furnished a 3:1:1 mixture of chloromethyl- (II), and dichloromethylpyridine (III) along with some unreacted starting material. Treatment of this mixture with NaI in refluxing acetone converted (II) into the iodomethyl compound (IV), but (I) and (III) remained unreacted. Then, the dialkylation of anthrone (V) in the presence of NaH in THF afforded the title compound, which was purified by column chromatography.

1 Earl, R.A.; Zaczek, R.; Teleha, C.A.; Fisher, B.N.; Maciag, C.M.; Marynowski, M.E.; Logue, A.R.; Tam, S.W.; Tinker, W.J.; Huang, S.M.; Chorvat, R.J.; 2-Fluoro-4-pyridinylmethyl analogues of linopirdine as orally active acetylcholine release-enhancing agents with good efficacy and duration of action. J Med Chem 1998, 41, 23, 4615.
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) 18296 2-Fluoro-4-methylpyridine 461-87-0 C6H6FN 详情 详情
(II) 18297 4-(chloromethyl)-2-fluoropyridine C6H5ClFN 详情 详情
(III) 18298 4-(dichloromethyl)-2-fluoropyridine C6H4Cl2FN 详情 详情
(IV) 18299 2-fluoro-4-(iodomethyl)pyridine C6H5FIN 详情 详情
(V) 18300 Anthrone; 9(10H)-anthracenone 90-44-8 C14H10O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(II)

The radical chlorination of 2-fluoro-4-methylpyridine (I) with NCS, benzoyl peroxide and acetic acid in refluxing acetonitrile gives a mixture of the starting material (I) and its mono (II) and dichloro (III) derivatives. This mixture of (I), (II) and (III) was treated with refluxing aqueous K2CO3 , which selectively hydrolyzes the monochloro derivative (II) to afford 2-fluoro-4-(hydroxymethyl)pyridine (IV). The compound (IV), which is easily separated from unreacted (I) and dichloro compound (III), is treated with methanesulfonyl chloride and TEA in ethyl acetate to provide the corresponding mesylate (V). The reaction of (V) with NaI in THF gives 2-fluoro-4-(iodomethyl)pyridine (VI), which is finally condensed with anthrone (VII) by means of lithium tert-butoxide in THF.

1 Pesti, J.A.; et al.; Efficient pyridinylmethyl functionalization: Synthesis of 10,10-bis[2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (DMP 543), an acetylcholine release enhancing agent. J Org Chem 2000, 65, 23, 7718.
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) 18296 2-Fluoro-4-methylpyridine 461-87-0 C6H6FN 详情 详情
(II) 18297 4-(chloromethyl)-2-fluoropyridine C6H5ClFN 详情 详情
(III) 18298 4-(dichloromethyl)-2-fluoropyridine C6H4Cl2FN 详情 详情
(IV) 50205 (2-fluoro-4-pyridinyl)methanol C6H6FNO 详情 详情
(V) 50206 (2-fluoro-4-pyridinyl)methyl methanesulfonate C7H8FNO3S 详情 详情
(VI) 18299 2-fluoro-4-(iodomethyl)pyridine C6H5FIN 详情 详情
(VII) 18300 Anthrone; 9(10H)-anthracenone 90-44-8 C14H10O 详情 详情
Extended Information