N-benzyl-2-methyl-2-propanamine -Drug Synthesis Database

【结构式】

【分子编号】24700

【品名】N-benzyl-2-methyl-2-propanamine

【CA登记号】3378-72-1

【分子式】C₁₁H₁₇N

【分子量】163.26272

【元素组成】C 80.93% H 10.5% N 8.58%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(V)

The reaction of 3,5-dihydroxyacetophenone (I) with N,N-dimethylcarbamoyl chloride (II) in hot pyridine gives 3,5-bis(N,N-dimethylcarbamoyloxy) acetophenone (III), which is brominated with Br2 in dioxane yielding 3,5-bis(N,N-dimethylcarbamoyloxy)phenacyl bromide (IV). The condensation of (IV) with N benzyl-tert butylamine (V) in refluxing acetone affords the corresponding w-amino derivative (VI), which is finally hydrogenated with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Olsson, O.A.T.; Svensson, L.A.; Wetterlin, K.I.L. (Draco Lakemedel AB); Bronchospamolytic carbamate derivatives. DD 202001; EP 0043807; JP 8240453; US 4419364; US 4451663 .
【2】 Castaner, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.

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)	24696	1-(3,5-dihydroxyphenyl)-1-ethanone	51863-60-6	C₈H₈O₃	详情	详情
(II)	13708	N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane	79-44-7	C₃H₆ClNO	详情	详情
(III)	24698	3-acetyl-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₁₄H₁₈N₂O₅	详情	详情
(IV)	24699	3-(2-bromoacetyl)-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₁₄H₁₇BrN₂O₅	详情	详情
(V)	24700	N-benzyl-2-methyl-2-propanamine	3378-72-1	C₁₁H₁₇N	详情	详情
(VI)	24701	3-[2-[benzyl(tert-butyl)amino]acetyl]-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₂₅H₃₃N₃O₅	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 reaction of methyl 5-bromoacetylsalicylate (I) with benzyl tert-butylamine (II) in methyl ethyl ketone gives methyl 5-(N-benzyl-N-tert-butyl-gycyl)salicylate (III), which is reduced with LiAlH4 in refluxing THF yielding alpha'-(N-benzyl-N-tert-butylami-nomethyl)-4-hydroxy-m-xylene-alpha,alpha'-diol (IV). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol-water.

参考文献中间体

合成目标

【1】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Hopkins, S.J.; Albuterol. Drugs Fut 1979, 4, 9, 629.
【2】 Lunts, L.H.C.; et al.; GB 1200886 .

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)	35836	methyl 5-(2-bromoacetyl)-2-hydroxybenzoate		C₁₀H₉BrO₄	详情	详情
(II)	24700	N-benzyl-2-methyl-2-propanamine	3378-72-1	C₁₁H₁₇N	详情	详情
(III)	39613	methyl 5-[2-[benzyl(tert-butyl)amino]acetyl]-2-hydroxybenzoate		C₂₁H₂₅NO₄	详情	详情
(IV)	39614	4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol		C₂₀H₂₇NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The chloromethylation of 4-hydroxyacetophenone (V) with formaldehyde and HCl in hot water gives 3-chloromethyl-4-hydroxyacetophenone (VI), which is treated with acetic anhydride-sodium acetate in refluxing acetic acid to afford 3-acetoxymethyl-4-acetoxyacetophenone (VII). The bromination of (VII) with Br2 in chloroform yields after hydrolysis 3-hydroxymethyl-4-hydroxyphenacyl bromide (VIII), which is condensed with benzyl tert-butylamine (II) in refluxing benzene giving alpha-(N-benzyl-N-tert-butylamino)-4-hydroxy-3-hydroxymethylacetophenone (IX). Finally, this compound is hydrogenated with H2 over Pd/C in ethanol. An alternative method of hydrogenation of (IX) is its reduction with NaBH4 - ethanol, to afford the previously obtained product (IV), which is reduced with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Lunts, L.H.C.; et al.; GB 1200886 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Hopkins, S.J.; Albuterol. Drugs Fut 1979, 4, 9, 629.
【3】 Collin, D.T.; et al.; Saligenin analogs of sympathomimetic catecholamines. J Med Chem 1970, 13, 4, 674-680.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	24700	N-benzyl-2-methyl-2-propanamine	3378-72-1	C₁₁H₁₇N	详情	详情
(IV)	39614	4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol		C₂₀H₂₇NO₃	详情	详情
(V)	18123	1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone	99-93-4	C₈H₈O₂	详情	详情
(VI)	39615	1-[3-(chloromethyl)-4-hydroxyphenyl]-1-ethanone		C₉H₉ClO₂	详情	详情
(VII)	39616	5-acetyl-2-(acetoxy)benzyl acetate		C₁₃H₁₄O₅	详情	详情
(VIII)	39617	2-bromo-1-[4-hydroxy-3-(hydroxymethyl)phenyl]-1-ethanone		C₉H₉BrO₃	详情	详情
(IX)	39618	2-[benzyl(tert-butyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl]-1-ethanone		C₂₀H₂₅NO₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

The reaction of 3-amino-4-benzyloxyacetophenone (I) with phosgene in toluene gives 3-isocyanate-4-benzyloxyacetophenone (II), which by reaction with ammonia in benzene yields 4-benzyloxy-3-ureidoacetophenone (III). The bromination of this product with Br2 in CHCl3 affords 4-benzyloxy-3-ureidophenacyl bromide (IV), amorphous product that is condensed with N-benzyl-N-tert-butylamine (V) in acetonitrile giving 4-benzyloxy-3-ureido-alpha-(N-benzyl-N-tert-butylamine)acetophenone hydrochloride (VI), m.p. 220-1 C. This product is finally hydrogenated with H2 over Pd/C in methanol

参考文献中间体

合成目标

【1】 Castaner, J.; Sungurbey, K.; Carbuterol. Drugs Fut 1976, 1, 9, 412.
【2】 Kaiser C.; et al. (Smith Kline French); DE 2106620 .

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)	20628	1-[3-amino-4-(benzyloxy)phenyl]-1-ethanone		C₁₅H₁₅NO₂	详情	详情
(II)	60749	1-[4-(benzyloxy)-3-isocyanatophenyl]-1-ethanone		C₁₆H₁₃NO₃	详情	详情
(III)	60750	N-[5-acetyl-2-(benzyloxy)phenyl]urea		C₁₆H₁₆N₂O₃	详情	详情
(IV)	60751	N-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]urea hydrobromide		C₁₆H₁₆Br₂N₂O₃	详情	详情
(V)	24700	N-benzyl-2-methyl-2-propanamine	3378-72-1	C₁₁H₁₇N	详情	详情
(VI)	60752	N-[5-{2-[benzyl(tert-butyl)amino]acetyl}-2-(benzyloxy)phenyl]urea		C₂₇H₃₁N₃O₃	详情	详情

Extended Information