1-(bromomethyl)-2,3,5-trichlorobenzene -Drug Synthesis Database

【结构式】

【分子编号】25672

【品名】1-(bromomethyl)-2,3,5-trichlorobenzene

【CA登记号】

【分子式】C₇H₄BrCl₃

【分子量】274.37086

【元素组成】C 30.64% H 1.47% Br 29.12% Cl 38.76%

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：(IX)

Regioselective lithiation of 1,2,4-trichlorobenzene (V) with n-BuLi at -60 C, followed by quenching of the resultant organolithium compound (VI) with N,N-dimethylformamide yielded 2,3,5-trichlorobenzaldehyde (VII) (1), which was then reduced with NaBH4 to provide alcohol (VIII). Bromination of (VIII) using PBr3 afforded compound (IX), whose bromide atom was displaced with KCN to give the trichlorophenylacetonitrile (X). Claisen condensation of (X) with ethyl formate in the presence of NaOEt furnished the oxo nitrile sodium enolate (XI), which was subsequently O-alkylated with iodomethane yielding the methoxy acrylonitrile (XII). Finally, cyclization of (XII) with the piperazine-1-carboxamidine (IV) in EtOH gave rise to the target pyrimidine derivative

参考文献中间体

合成目标

【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 .
【2】 Patel, R.; Packham, T.W.; Germain, A.L.; Barras, J.R.; Milne, D.J. (GlaxoSmithKline plc); Process of preparing 2,3,5-trihalobenzaldehyde. WO 9507877 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	62330			C₇H₁₈N₄	详情	详情
(V)	62331	1,2,4-trichlorobenzene		C₆H₃Cl₃	详情	详情
(VI)	62332	(2,3,5-trichlorophenyl)lithium		C₆H₂Cl₃Li	详情	详情
(VII)	25670	2,3,5-trichlorobenzaldehyde	56961-75-2	C₇H₃Cl₃O	详情	详情
(VIII)	25671	(2,3,5-trichlorophenyl)methanol		C₇H₅Cl₃O	详情	详情
(IX)	25672	1-(bromomethyl)-2,3,5-trichlorobenzene		C₇H₄BrCl₃	详情	详情
(X)	25673	2-(2,3,5-trichlorophenyl)acetonitrile		C₈H₄Cl₃N	详情	详情
(XI)	62333	sodium (Z)-2-cyano-2-(2,3,5-trichlorophenyl)-1-ethenolate		C₉H₃Cl₃NNaO	详情	详情
(XII)	62334	(E)-3-methoxy-2-(2,3,5-trichlorophenyl)-2-propenenitrile		C₁₀H₆Cl₃NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

2,3,5-Trichlorobenzaldehyde (I) was reduced with NaBH4 to the benzyl alcohol (II) and then converted to the corresponding bromide (III) by means of PBr3 in benzene. Displacement of bromide group of (III) with KCN gave 2,3,5-trichlorophenylacetonitrile (IV), which was condensed with ethyl diethoxyacetate (V) in the presence of NaOEt to provide keto nitrile (VI). Subsequent treatment of (VI) with ethereal diazomethane generated the enol ether (VII). This was cyclized with guanidine (VIII) in boiling EtOH to produce pyrimidine (IX). After ketal hydrolysis of (IX), the resulting aldehyde (X) was reduced with NaBH4 to alcohol (XI). Finally, treatment of (XI) with diethylaminosulfur trifluoride in cold CH2Cl2 provided the desired fluoromethyl compound.

参考文献中间体

合成目标

【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 .

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)	25670	2,3,5-trichlorobenzaldehyde	56961-75-2	C₇H₃Cl₃O	详情	详情
(II)	25671	(2,3,5-trichlorophenyl)methanol		C₇H₅Cl₃O	详情	详情
(III)	25672	1-(bromomethyl)-2,3,5-trichlorobenzene		C₇H₄BrCl₃	详情	详情
(IV)	25673	2-(2,3,5-trichlorophenyl)acetonitrile		C₈H₄Cl₃N	详情	详情
(V)	25674	ethyl 2,2-diethoxyacetate	6065-82-3	C₈H₁₆O₄	详情	详情
(VI)	25675	4,4-diethoxy-3-oxo-2-(2,3,5-trichlorophenyl)butanenitrile		C₁₄H₁₄Cl₃NO₃	详情	详情
(VII)	25676	(E)-4,4-diethoxy-3-methoxy-2-(2,3,5-trichlorophenyl)-2-butenenitrile		C₁₅H₁₆Cl₃NO₃	详情	详情
(VIII)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(IX)	25677	2-amino-6-(diethoxymethyl)-5-(2,3,5-trichlorophenyl)-4-pyrimidinylamine		C₁₅H₁₇Cl₃N₄O₂	详情	详情
(X)	25678	2,6-diamino-5-(2,3,5-trichlorophenyl)-4-pyrimidinecarbaldehyde		C₁₁H₇Cl₃N₄O	详情	详情
(XI)	25679	[2,6-diamino-5-(2,3,5-trichlorophenyl)-4-pyrimidinyl]methanol		C₁₁H₉Cl₃N₄O	详情	详情

Extended Information