4-(chloromethyl)-2-fluoropyridine -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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