(3,5-dichlorophenyl)methanol -Drug Synthesis Database

【结构式】

【分子编号】24168

【品名】(3,5-dichlorophenyl)methanol

【CA登记号】60211-57-6

【分子式】C₇H₆Cl₂O

【分子量】177.02944

【元素组成】C 47.49% H 3.42% Cl 40.05% O 9.04%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

Reduction of 3,5-dichlorobenzoyl chloride (I) with NaBH4 in THF in the presence of N-methyl pyrrolidone (NMP) provides benzyl alcohol derivative (II), which is then treated with tert-butyl dimethylsilyl chloride (TBDMSCl) in DMF in the presence of imidazole and DMAP to furnish protected compound (III). Lithiation of (III) with BuLi (occasionally in the presence of tetramethylethylenediamine) in THF followed by reaction with p-chlorobenzoyl chloride (IV) in THF affords benzophenone derivative (V), which is then deprotected by means of concentrated HCl to yield benzyl alcohol derivative (VI). Conversion of alcohol (VI) into chloride (VII) is then performed by reaction with SOCl2. Next, reaction of (VII) with NaN3 and NaI in refluxing ethanol gives benzylazide derivative (VIII), which is finally converted into the desired product by reaction with cyanoacetamide (IX) and K2CO3 in DMSO.

参考文献中间体

合成目标

【1】 Bochis, R.J.; Chabala, J.C.; Fisher, M.H. (Merck & Co., Inc.); 5-(Amino or substd.amino)-1,2,3-triazoles. EP 0151529; JP 1985188376; US 4590201 .
【2】 Hube, D. (Merck & Co., Inc.); 5-Amino or substd. amino-1,2,3-triazoles useful as anti-metastasis agents. JP 1991056417; US 5045543 .
【3】 Hupe, D.; Azzolina, B.A.; Argenbright, L.; Behrens, N. (Merck & Co., Inc.); 5-Amino or substd. amino 1,2,3-triazoles useful as antiproliferative agents. EP 0304221; JP 1989068321; US 4847257 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	49483	N,N,N',N'-Tetramehylenediamine; 1,2-Bis(dimethylamino)ethane		C₆H₁₆N₂	详情	详情
(I)	27769	3,5-dichlorobenzoyl chloride	2905-62-6	C₇H₃Cl₃O	详情	详情
(II)	24168	(3,5-dichlorophenyl)methanol	60211-57-6	C₇H₆Cl₂O	详情	详情
(III)	49482	tert-butyl(dimethyl)silyl 3,5-dichlorobenzyl ether; tert-butyl[(3,5-dichlorobenzyl)oxy]dimethylsilane		C₁₃H₂₀Cl₂OSi	详情	详情
(IV)	10295	p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride	122-01-0	C₇H₄Cl₂O	详情	详情
(V)	49484	[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2,6-dichlorophenyl](4-chlorophenyl)methanone		C₂₀H₂₃Cl₃O₂Si	详情	详情
(VI)	49485	(4-chlorophenyl)[2,6-dichloro-4-(hydroxymethyl)phenyl]methanone		C₁₄H₉Cl₃O₂	详情	详情
(VII)	49486	(4-chlorophenyl)[2,6-dichloro-4-(chloromethyl)phenyl]methanone		C₁₄H₈Cl₄O	详情	详情
(VIII)	49487	[4-(azidomethyl)-2,6-dichlorophenyl](4-chlorophenyl)methanone		C₁₄H₈Cl₃N₃O	详情	详情
(IX)	12122	Cyanoacetamide; 2-Cyanoacetamide	107-91-5	C₃H₄N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

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

Extended Information