D-2343, -Drug Synthesis Database

【结构式】

【药物名称】D-2343

【化学名称】1-(4-Hydroxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl)propylamino]ethanol hydrochloride
　　　　　　4-Hydroxy-alpha-[[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]amino]methyl]benzenemethanol hydrochloride

【CA登记号】72734-58-8, 72734-63-5 (free base)

【分子式】C₂₀H₂₈ClNO₃

【分子量】365.90406

【开发单位】AstraZeneca (Originator)

【药理作用】Asthma Therapy, Bronchodilators, RESPIRATORY DRUGS

合成路线1 合成路线2 合成路线3

合成路线1

The condensation of acetone (VIII) with 2-methoxybenzaldehyde (IX) by means of NaOH gives 2-methoxybenzalacetone (X), which is reduced with H2 over Raney-Ni in ethanol to yield 4-(2-methoxyphenyl)-2-butanone (XI). The Grignard reaction of (XI) with methylmagnesium iodide in ether affords 1,1-dimethyl-3-(2-methoxyphenyl) propanol (XII), which by reaction with NaCN by means of H2SO4 in acetic acid affords N-[1,1-dimethyl-3-(2-methoxyphenyl)propyl]formamide (XIII). Finally, this compound is hydrolyzed with refluxing 5N NaOH to give (II).

参考文献中间体

【1】 Olsson, O.A.T.; Persson, N.H.A.; Svensson, L.A.; Waldeck, C.B.; Wetterlin, K.J.L.; EP 0004835 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; D-2343. Drugs Fut 1982, 7, 1, 17.

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)	36422	3-(2-methoxyphenyl)-1,1-dimethylpropylamine; 4-(2-methoxyphenyl)-2-methyl-2-butanamine		C₁₂H₁₉NO	详情	详情
(VIII)	23199	2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether	67-64-1	C₃H₆O	详情	详情
(IX)	12568	2-Methoxybenzaldehyde; o-Methoxybenzaldehyde	135-02-4	C₈H₈O₂	详情	详情
(X)	36418	(E)-4-(2-methoxyphenyl)-3-buten-2-one		C₁₁H₁₂O₂	详情	详情
(XI)	36419	4-(2-methoxyphenyl)-2-butanone		C₁₁H₁₄O₂	详情	详情
(XII)	36420	4-(2-methoxyphenyl)-2-methyl-2-butanol		C₁₂H₁₈O₂	详情	详情
(XIII)	36421	3-(2-methoxyphenyl)-1,1-dimethylpropylformamide		C₁₃H₁₉NO₂	详情	详情

合成路线2

The bromination of 4-benzyloxyacetophenone (VI) with Br2 in dioxane gives 4-benzyloxyphenacyl bromide (VII), which by reduction with NaBH4 in dioxane and epoxidation with NaOH water is converted into (I). The condensation of 4-benzyloxystyrene oxide (I) with 1,1-dimethyl-3-(2-methoxyphenyl)propylamine (II) in refluxing isopropanol gives 1-(4-benzyloxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl)propylamino]ethanol (III), which is debenzylated by reduction with H2 over Pd/C in ethanol, and treated with HCl.

参考文献中间体

【1】 Olsson, O.A.T.; Persson, N.H.A.; Svensson, L.A.; Waldeck, C.B.; Wetterlin, K.J.L.; EP 0004835 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; D-2343. Drugs Fut 1982, 7, 1, 17.

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)	36425	2-[4-(benzyloxy)phenyl]oxirane; benzyl 4-(2-oxiranyl)phenyl ether		C₁₅H₁₄O₂	详情	详情
(II)	36422	3-(2-methoxyphenyl)-1,1-dimethylpropylamine; 4-(2-methoxyphenyl)-2-methyl-2-butanamine		C₁₂H₁₉NO	详情	详情
(III)	36426	1-[4-(benzyloxy)phenyl]-2-[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]amino]-1-ethanol		C₂₇H₃₃NO₃	详情	详情
(VI)	36423	1-[4-(benzyloxy)phenyl]-1-ethanone	54696-05-8	C₁₅H₁₄O₂	详情	详情
(VII)	36424	1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone		C₁₅H₁₃BrO₂	详情	详情

合成路线3

The oxidation of (VI) with SeO2 in hot dioxane-water gives 4-benzyloxyphenylglyoxal (IV). The condensation with (II) in refluxing ethanol, gives 4-benzyloxy-alpha-[1,1-dimethyl-3-(2-methoxyphenyl)propylimino]acetophenone (V), which is then reduced with NaBH4 in ethanol to afford (III), which is debenzylated by reduction with H2 over Pd/C in ethanol, and treated with HCl.

参考文献中间体

【1】 Olsson, O.A.T.; Persson, N.H.A.; Svensson, L.A.; Waldeck, C.B.; Wetterlin, K.J.L.; EP 0004835 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; D-2343. Drugs Fut 1982, 7, 1, 17.

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)	36422	3-(2-methoxyphenyl)-1,1-dimethylpropylamine; 4-(2-methoxyphenyl)-2-methyl-2-butanamine		C₁₂H₁₉NO	详情	详情
(III)	36426	1-[4-(benzyloxy)phenyl]-2-[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]amino]-1-ethanol		C₂₇H₃₃NO₃	详情	详情
(IV)	31696	2-[4-(benzyloxy)phenyl]-2-oxoacetaldehyde; 4-benzyloxy-alpha-oxophenylacetaldehyde		C₁₅H₁₂O₃	详情	详情
(V)	36427	1-[4-(benzyloxy)phenyl]-2-[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]imino]-1-ethanone		C₂₇H₂₉NO₃	详情	详情
(VI)	36423	1-[4-(benzyloxy)phenyl]-1-ethanone	54696-05-8	C₁₅H₁₄O₂	详情	详情

Extended Information