3,5-dichlorobenzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】24169

【品名】3,5-dichlorobenzaldehyde

【CA登记号】10203-08-4

【分子式】C₇H₄Cl₂O

【分子量】175.01356

【元素组成】C 48.04% H 2.3% Cl 40.51% O 9.14%

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：(III)

3,5-Dichlorobenzoic acid (I) is reduced with LiAlH4 to give 3,5-dichlorobenzyl alcohol (II). The latter is selectively oxidized with MnO2, yielding 3,5-dichlorobenzaldehyde (III). The condensation of (III) with methylamine gives the corresponding imine (IV), which can be reduced to the benzylamine (V) either with LiAlH4 or NaBH4. The hydrochloride is precipitated with etheric HCl.

参考文献中间体

合成目标

【1】 Meindl, W.R.; et al.; Benzylamines: Synthesis and evaluation of antimycobacterial properties. J Med Chem 1984, 27, 9, 1111.
【2】 Meindl, W.; Schonenberger, H.; Seydel, J.K.; Dhople, A.M.; ME-93. Drugs Fut 1987, 12, 12, 1108.

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)	24167	3,5-dichlorobenzoic acid	51-36-5	C₇H₄Cl₂O₂	详情	详情
(II)	24168	(3,5-dichlorophenyl)methanol	60211-57-6	C₇H₆Cl₂O	详情	详情
(III)	24169	3,5-dichlorobenzaldehyde	10203-08-4	C₇H₄Cl₂O	详情	详情
(IV)	24170	N-[(E)-(3,5-dichlorophenyl)methylidene]-N-methylamine		C₈H₇Cl₂N	详情	详情
(V)	24171	(3,5-dichlorophenyl)-N-methylmethanamine		C₈H₉Cl₂N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

A process useful for the industrial preparation of eberconazole has been reported: The Wittig condensation of 2-(methoxycarbonyl)benzyl(triphenyl)phosphonium bromide (I) with 3,5-dichlorobenzaldehyde (II) by means of NaH in DMF gives 2-[2-(3,5-dichlorophenyl)vinyl]benzoic acid methyl ester (III), which is hydrolyzed with NaOH in methanol to the corresponding free acid (IV). The hydrogenation of (IV) with H2 over Pd/C in methanol affords 2-[2-(3,5-dichlorophenyl)ethyl]benzoic acid (V), which is cyclized to 2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one (VI) by means of polyphosphoric acid. The reduction of (VI) with NaBH4 yields the corresponding carbinol (VII), which is treated with SOCl2 affording the chloride (VIII). Finally, this compound is condensed with imidazole (IX) in refluxing DMF.

参考文献中间体

合成目标

【1】 Farrerons Gallemi, C.; Monserrat Vidal, C.; Miquel Bono, I.J. (Laboratorios Salvat SA); Process for the preparation of eberconazol and intermediates thereof. WO 9921838 .

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)	26013	[2-(methoxycarbonyl)benzyl](triphenyl)phosphonium bromide		C₂₇H₂₄BrO₂P	详情	详情
(II)	24169	3,5-dichlorobenzaldehyde	10203-08-4	C₇H₄Cl₂O	详情	详情
(III)	26014	methyl 2-[(E)-2-(3,5-dichlorophenyl)ethenyl]benzoate		C₁₆H₁₂Cl₂O₂	详情	详情
(IV)	26015	2-[(E)-2-(3,5-dichlorophenyl)ethenyl]benzoic acid		C₁₅H₁₀Cl₂O₂	详情	详情
(V)	26016	2-(3,5-dichlorophenethyl)benzoic acid		C₁₅H₁₂Cl₂O₂	详情	详情
(VI)	14362	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one		C₁₅H₁₀Cl₂O	详情	详情
(VII)	14363	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol		C₁₅H₁₂Cl₂O	详情	详情
(VIII)	14364	2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₅H₁₁Cl₃	详情	详情
(IX)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The reaction of 3,5-dichlorobenzaldehyde (I) with malonic acid and ammonium acetate in refluxing isopropanol gives 3-amino-3-(3,5-dichlorophenyl)propionic acid (II), which is esterified with ethanol and HCl yielding the ethyl ester (III), The condensation of (III) with N-(tert-butoxycarbonyl)glycine succinimidyl ester (IV) by means of TEA in THF affords the glycinamide (V), which is deprotected with HCl in dioxane to afford intermediate (VI). The free amino group of (VI) is then acylated with 3-guanidinobenzoic acid by means of isobutyl chloroformate and NMM in DMF yielding the ethyl ester (VIII) of the target product, which is finally hydrolyzed with LiOH in water.

参考文献中间体

合成目标

【1】 Ruminski, P.G.; Clare, M.; Collins, P.W.; Desai, B.N.; Lindmark, R.J.; Rico, J.G.; Rogers, T.E.; Russell, M.A. (Pharmacia Corp.); Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivs. as integrin antagonists. EP 0850221; JP 1999510814; US 6013651; WO 9708145 .

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)	24169	3,5-dichlorobenzaldehyde	10203-08-4	C₇H₄Cl₂O	详情	详情
(II)	28352	3-(3,5-dichlorophenyl)-beta-alanine		C₉H₉Cl₂NO₂	详情	详情
(III)	28353	ethyl 3-amino-3-(3,5-dichlorophenyl)propanoate		C₁₁H₁₃Cl₂NO₂	详情	详情
(IV)	16364	tert-butyl N-[2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethyl]carbamate; N-T-BOC-glycine N-hydroxysuccinimide ester	3392-07-2	C₁₁H₁₆N₂O₆	详情	详情
(V)	28354	ethyl 3-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)-3-(3,5-dichlorophenyl)propanoate		C₁₈H₂₄Cl₂N₂O₅	详情	详情
(VI)	28355	ethyl 3-[(2-aminoacetyl)amino]-3-(3,5-dichlorophenyl)propanoate		C₁₃H₁₆Cl₂N₂O₃	详情	详情
(VII)	28356	3-[[amino(imino)methyl]amino]benzoic acid		C₈H₉N₃O₂	详情	详情
(VIII)	28357	ethyl 3-([2-[(3-[[amino(imino)methyl]amino]benzoyl)amino]acetyl]amino)-3-(3,5-dichlorophenyl)propanoate		C₂₁H₂₃Cl₂N₅O₄	详情	详情

Extended Information