N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine -Drug Synthesis Database

【结构式】

【分子编号】30353

【品名】N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine

【CA登记号】

【分子式】C₁₇H₂₁N

【分子量】239.36048

【元素组成】C 85.31% H 8.84% N 5.85%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The addition of N-benzyl-3-phenyl-1-methylpropylamine (I) to ethyl 4-(2,3-oxidopropoxy)phenylacetate (II) in refluxing ethanol, followed by debenzylation with H2 over Pd/C gives 1-[4-(ethoxycarbonylmethyl)phenoxyl-3-(1-methyl-3-phenylpropylamino)-2-propanol (III), which is then treated with NH3 in ethanol.

参考文献中间体

合成目标

【1】 Takizawa, H.; Oiji, Y.; Kubo, K. (Kyowa Hakko Kogyo Co., Ltd.); Amino-alcohol derivatives. DE 3010752; US 4381398 .
【2】 Castaner, J.; Serradell, M.N.; KF-4317. Drugs Fut 1984, 9, 3, 189.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	30352	ethyl 2-[4-(2-oxiranylmethoxy)phenyl]acetate	C₁₃H₁₆O₄	详情	详情
(II)	30353	N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine	C₁₇H₂₁N	详情	详情
(III)	30354	ethyl 2-(4-[2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy]phenyl)acetate	C₂₃H₃₁NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reaction of 5-acetylsalicylamide (I) with benzyl chloride (II) by means of sodium methoxide in hot DMF gives 4-benzyloxy-3-carbamoylacetophenone (III), which by bromination with Br2 in refluxing CHCl3 is converted into 4-benzyloxy-3-carbamoylphenacyl bromide (IV). The condensation of (IV) with N-(4-phenyl-2-butyl)benzylamine (V) (prepared from benzylamine (VI) and 4-phenyl-2-butanone (VII), p-toluenesulfonic acid and NaBH4 in benzene -methanol) by means of K2CO3 in DMF yields 2-benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide (VIII), which is reduced with NaBH4 in ethanol to afford 2-benzyloxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)-N-benzylamino]ethyl]benzamide (IX). Finally, this compound is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol. The separation into its optical isomers is performed by conventional methods.

参考文献中间体

合成目标

【1】 Gold, E.H.; Chang, W. (Schering Corp.); A phenylalkylaminoethylsalicylamide, its preparation and pharmaceutical compositions containing it. CA 1151211; DD 150457; EP 0009702; JP 55055147; ZA 7904872 .
【2】 Gold, E.H.; Chang, W. (Schering Biotech Corp.); Diastereoisomers of 5-(1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl)salicylamide. US 4173583 .
【3】 Serradell, M.N.; Castaner, J.; Weetman, D.F.; Blancafort, P.; Sch-19,927. Drugs Fut 1982, 7, 11, 815.

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)	32058	5-Acetyl-2-hydroxybenzamide; 5-Acetylsalicylamide	40187-51-7	C₉H₉NO₃	详情	详情
(II)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(III)	32059	4-Benzyloxy-3-carbamoylacetophenone; 5-Acetyl-2-(benzyloxy)benzamide		C₁₆H₁₅NO₃	详情	详情
(IV)	32060	2-(Benzyloxy)-5-(2-bromoacetyl)benzamide; 4-Benzyloxy-3-carbamoylphenacyl bromide; 2-Benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide		C₁₆H₁₄BrNO₃	详情	详情
(V)	30353	N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine		C₁₇H₂₁N	详情	详情
(VI)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(VII)	32061	4-phenyl-2-butanone	2550-26-7	C₁₀H₁₂O	详情	详情
(VIII)	32060	2-(Benzyloxy)-5-(2-bromoacetyl)benzamide; 4-Benzyloxy-3-carbamoylphenacyl bromide; 2-Benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide		C₁₆H₁₄BrNO₃	详情	详情
(IX)	32063	5-[2-[Benzyl(1-methyl-3-phenylpropyl)amino]-1-hydroxyethyl]-2-(benzyloxy)benzamide; 2-Benzyloxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)-N-benzylamino]ethyl]benzamide		C₃₃H₃₆N₂O₃	详情	详情
(X)	32064	2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide	36894-69-6	C₁₉H₂₄N₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Condensation of 5-bromoacetylsalicylamide (I) with N-benzyl-N-(1-methyl-3-phenylpropyl)amine (II) in refluxing butanone to 5-(N-benzyl-N-(1-methyl-3-phenylpropyl) glycyl)salicylamide hydrochloride (III), m.p. 139-141 C, which is reduced with H2 over Pt-Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Castaner, J.; Blancafort, P.; Labetalol. Drugs Fut 1976, 1, 3, 125.
【2】 Lunts, L.H.; et al.; 1-Phenyl-2-aminoethanol derivatives bronchodilators. DE 1643224; FR 1557677; FR 8010M; GB 1200886; US 3642896; US 3644353; US 3705233 .

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)	30353	N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine		C₁₇H₂₁N	详情	详情
(II)	40347	5-(2-bromoacetyl)-2-hydroxybenzamide; 5-Bromoacetylsalicylamide	73866-23-6	C₉H₈BrNO₃	详情	详情
(III)	40348	5-[2-[benzyl(1-methyl-3-phenylpropyl)amino]acetyl]-2-hydroxybenzamide		C₂₆H₂₈N₂O₃	详情	详情

Extended Information