Encainide, MJ-9067-1(hydrochloride), MJ-9067, Enkaid, -Drug Synthesis Database

【结构式】

【药物名称】Encainide, MJ-9067-1(hydrochloride), MJ-9067, Enkaid

【化学名称】(±)-4-Methoxy-N-[2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl]benzamide

【CA登记号】37612-13-8, 66794-74-9 (HCl)

【分子式】C₂₂H₂₈N₂O₂

【分子量】352.48066

【开发单位】Bristol-Myers Squibb (Originator)

【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS

合成路线1 合成路线2

合成路线1

A new method for the synthesis of encainide has been reported: The acylation of methyl anthranilate (I) with 4-anisoyl chloride (II) by means of NaOH in methylene chloride gives methyl N-(p-anisoyl)anthranilate (III), which is condensed with 2-picoline (IV) by means of n-butyllithium in THF yielding 2-(2-pyridylacetyl)-p-anisanilide (V). Finally, this compound is reduced with H2 over Pt/C then with Pd/C, treated with formaldehyde and reduced again with H2 over Pt/C.

参考文献中间体

【1】 Madding, G.D. (Bristol-Myers Squibb Co.); Process for production of encainide. JP 58105963; NL 8204775; US 4394507 .

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)	11161	methyl 2-aminobenzoate; Methyl anthranilate	134-20-3	C₈H₉NO₂	详情	详情
(II)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(III)	29100	methyl 2-[(4-methoxybenzoyl)amino]benzoate		C₁₆H₁₅NO₄	详情	详情
(IV)	17590	2-methylpyridine; 2-picoline	109-06-8	C₆H₇N	详情	详情
(V)	29101	4-methoxy-N-[2-[2-(2-pyridinyl)acetyl]phenyl]benzamide		C₂₁H₁₈N₂O₃	详情	详情

合成路线2

The condensation of 2-methylpyridine (I) with 2-nitrobenzaldehyde (II) in acetic anhydride gives 2-(2-nitrostyryl)pyridine (III), which is quaternized with methyl iodide in refluxing acetone yielding 2-(2-nitrostyryl)-1-methylpyridinium iodide (IV) . The reduction of (IV) with H2 over PtO2 in ethanol affords 2-(2-aminophenethyl)-1-methylpiperidine (V), which is then acylated with 4-methoxybenzoyl chloride (A) in pyridine.

参考文献中间体

【1】 Dykstra, S.J.; Minielli, J.L.; Substituted piperidines and a process for the preparation thereof. BE 0779951; CA 961038; CH 578529; DE 2210154; FR 2128584; GB 1346261; NL 161443C; NL 7202614 .
【2】 Kendrick, W.D.; Ferguson, H.C.; acid and quimidine analogs. 2-(o-Acylaminophenethyl)piperidines. J Med Chem 1973, 16, 9, 1015.
【3】 Castaner, J.; MJ 9067. Drugs Fut 1977, 2, 3, 176.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(I)	17590	2-methylpyridine; 2-picoline	109-06-8	C₆H₇N	详情	详情
(II)	11370	2-Nitrobenzaldehyde	552-89-6	C₇H₅NO₃	详情	详情
(III)	40197	2-[(E)-2-(2-nitrophenyl)ethenyl]pyridine		C₁₃H₁₀N₂O₂	详情	详情
(IV)	40198	1-methyl-2-[(E)-2-(2-nitrophenyl)ethenyl]pyridinium iodide		C₁₄H₁₃IN₂O₂	详情	详情
(V)	40199	2-[2-(1-methyl-2-piperidinyl)ethyl]phenylamine; 2-[2-(1-methyl-2-piperidinyl)ethyl]aniline		C₁₄H₂₂N₂	详情	详情

Extended Information