N-(2-pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide -Drug Synthesis Database

【结构式】

【分子编号】33970

【品名】N-(2-pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide

【CA登记号】

【分子式】C₁₇H₁₄F₆N₂O₃

【分子量】408.3002592

【元素组成】C 50.01% H 3.46% F 27.92% N 6.86% O 11.76%

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：(III)

The condensation of 2-aminomethylpyridine (II) with 2,2,2-trifluoroethyl-2,5-bis(2,2,2-trifluoroethoxy)benzoate (I) in refluxing glyme gives 2,5-bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)benzamide (III), which is then hydrogenated with H2 over Pd/C in acetic acid.

参考文献中间体

合成目标

【1】 Bannitt, E.H.; Bronn, W.R.; Derivatives of pyrrolidine and piperidine. ES 435870; FR 2265366; GB 1508015; JP 58065268; US 3900481 .
【2】 Hillier, K.; Castaner, J.; Flecainide acetate. Drugs Fut 1977, 2, 9, 586.

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)	33962	2-(benzyloxy)-2-oxoethyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate		C₂₈H₂₄ClNO₆	详情	详情
(II)	13582	2-Pyridinylmethanamine; 2-Pyridinylmethylamine; 2-(Aminomethyl)pyridine	3731-51-9	C₆H₈N₂	详情	详情
(III)	33970	N-(2-pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide		C₁₇H₁₄F₆N₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The etherification of hydroquinone (I) with 2,2,2-trifluoroethyl trifluoromethanesulfonate (II) by means of K2CO3 in refluxing acetone gives the corresponding diether (III), which is submitted to a Friedel-Crafts condensation with Ac-Cl or Ac2O and AlCl3 in dichloromethane yielding the acetophenone (IV). The chlorination of (IV) with Cl2 in acetic acid at 55 C gives the alpha, alpha-dichloroacetophenone (V), which is further chlorinated with Cl2 and NaOAc in acetic acid at 100 C affording the corresponding trichloro derivative (VI). The reaction of (VI) with 2-(aminomethyl)pyridine (VII) in cyclohexane/toluene or isopropanol furnishes the benzamide (VIII), which is finally hydrogenated with H2 over Pt/C in isopropanol/acetic acid to give the target piperidine derivative.

参考文献中间体

合成目标

【1】 Leir, C.M. (3M Pharmaceuticals); Process for the preparation of derivs. of pyrrolidine and piperidine. US 4642384 .

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)	13163	p-Dihydrobenzene; Hydroquinone	123-31-9	C₆H₆O₂	详情	详情
(II)	40675	2,2,2-trifluoroethyl trifluoromethanesulfonate	6226-25-1	C₃H₂F₆O₃S	详情	详情
(III)	40737	1,4-bis(2,2,2-trifluoroethoxy)benzene; 4-(2,2,2-trifluoroethoxy)phenyl 2,2,2-trifluoroethyl ether	66300-61-6	C₁₀H₈F₆O₂	详情	详情
(IV)	40738	1-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1-ethanone	76784-40-2	C₁₂H₁₀F₆O₃	详情	详情
(V)	40739	1-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-2,2-dichloro-1-ethanone		C₁₂H₈Cl₂F₆O₃	详情	详情
(VI)	40740	1-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-2,2,2-trichloro-1-ethanone	76784-42-4	C₁₂H₇Cl₃F₆O₃	详情	详情
(VII)	13582	2-Pyridinylmethanamine; 2-Pyridinylmethylamine; 2-(Aminomethyl)pyridine	3731-51-9	C₆H₈N₂	详情	详情
(VIII)	33970	N-(2-pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide		C₁₇H₁₄F₆N₂O₃	详情	详情
(IX)	18983	1,4-dibromobenzene	106-37-6	C₆H₄Br₂	详情	详情
(X)	19483	2,2,2-trifluoro-1-ethanol	75-89-8	C₂H₃F₃O	详情	详情

Extended Information