N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline -Drug Synthesis Database

【结构式】

【分子编号】33475

【品名】N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline

【CA登记号】

【分子式】C₈H₇ClF₃N

【分子量】209.5982296

【元素组成】C 45.84% H 3.37% Cl 16.91% F 27.19% N 6.68%

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：(VI)

The alkylation of p-chloroaniline (V) as before yields N-(2,2,2-trifluoroethyl)aniline (VI), which is then condensed with aziridine (C) affording the substituted aniline (VII). The benzoylation of (VII) with 2-fluorobenzoyl chloride (D) yields the amide (VIII), which is cyclized with P2O5 in refluxing POCl3 giving 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine (IX). This compound is oxidized with RuO4 in CCl4 to give 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I), which by reaction with P2S5 in refluxing dioxane gives the target compound.

参考文献中间体

合成目标

【1】 Steinman, M.; Benzodiazepines and the process for their manufacture. DE 2138773; ES 393953; FR 2102114; GB 1345938 .
【2】 Steinman, M.; 1-Polyfluoroalkyl-1,4-benzodiazepin-2-thiones for effecting tranquilization, sedation and treating colvulsions. US 3920818 .
【3】 Castaner, J.; Thorpe, P.; Quazepam. Drugs Fut 1978, 3, 2, 139.
【4】 Topliss, J.G.; Steinman, M.; Alekel, R.; Wong, Y.S.; York, E.E.; 1-Polyfluoroalkylbenzodiazepines. J Med Chem 1973, 16, 12, 1354-60.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(D)	19551	2-Fluorobenzoyl chloride	393-52-2	C₇H₄ClFO	详情	详情
(A)	33474	2,2,2-Trifluoroethyl trichloromethanesulfonate; 2,2,2-Trifluoroethyl trichloromethylsulfonate	23199-56-6	C₃H₂Cl₃F₃O₃S	详情	详情
(I)	33471	7-Chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₁₇H₁₁ClF₄N₂O	详情	详情
(V)	12034	4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline	106-47-8	C₆H₆ClN	详情	详情
(VI)	33475	N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline		C₈H₇ClF₃N	详情	详情
(VII)	33476	N(1)-(4-chlorophenyl)-N(1)-(2,2,2-trifluoroethyl)-1,2-ethanediamine; N-(2-aminoethyl)-N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine		C₁₀H₁₂ClF₃N₂	详情	详情
(VIII)	33477	N-[2-[4-chloro(2,2,2-trifluoroethyl)anilino]ethyl]-2-fluorobenzamide		C₁₇H₁₅ClF₄N₂O	详情	详情
(IX)	33478	7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine; 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine		C₁₇H₁₃ClF₄N₂	详情	详情
(C)	10151	Ethyleneimine; Aziridine; Azirane	151-56-4	C₂H₅N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

N-trifluoroethyl derivative (III) can also be obtained by alkylation of (X) with (II) in refluxing xylene giving 4-chloro-N-(2,2,2-trifluoroethyl)aniline (XV), followed by a Friedel-Crafts reaction with benzoyl chloride by means of AlCl3.

参考文献中间体

合成目标

【1】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .
【2】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .

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)	33474	2,2,2-Trifluoroethyl trichloromethanesulfonate; 2,2,2-Trifluoroethyl trichloromethylsulfonate	23199-56-6	C₃H₂Cl₃F₃O₃S	详情	详情
(III)	33848	[5-chloro-2-[(2,2,2-trifluoroethyl)amino]phenyl](phenyl)methanone		C₁₅H₁₁ClF₃NO	详情	详情
(X)	12034	4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline	106-47-8	C₆H₆ClN	详情	详情
(XV)	33475	N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline		C₈H₇ClF₃N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XV)

N-bromoacetyl compound (IV) can also be obtained by bromoacetylation of (XV) with bromoacetyl bromide (B) in refluxing benzene affording 4-chloro-N-bromoacetyl-N-(2,2,2-trifluoroethyl)aniline (XVI), followed by a Friedel-Crafts reaction with benzoyl chloride by means of AlCl3.

参考文献中间体

合成目标

【1】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .
【2】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(D)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(B)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(IV)	33849	N-(2-benzoyl-4-chlorophenyl)-2-bromo-N-(2,2,2-trifluoroethyl)acetamide		C₁₇H₁₂BrClF₃NO₂	详情	详情
(XV)	33475	N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline		C₈H₇ClF₃N	详情	详情
(XVI)	33852	2-bromo-N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)acetamide		C₁₀H₈BrClF₃NO	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 4-chloro-N-(2,2,2-trifluoroethyl)aniline (V) with ethyleneimine (C) by means of AlCl3 in benzene affords the N-(2-aminoethyl) compound (VI), which is benzoylated with benzoyl chloride (D) as usual yielding the benzamide (VII). Compound (VII) is cyclized with P2O5 in POCl3 giving 7-chloro-1,2-dihydro-5-phenyl-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine (VIII), which is finally oxidized with RuO4.

参考文献中间体

合成目标

【1】 Topliss, J.G.; Steinman, M.; Alekel, R.; Wong, Y.S.; York, E.E.; 1-Polyfluoroalkylbenzodiazepines. J Med Chem 1973, 16, 12, 1354-60.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(D)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(V)	33475	N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline		C₈H₇ClF₃N	详情	详情
(VI)	33476	N(1)-(4-chlorophenyl)-N(1)-(2,2,2-trifluoroethyl)-1,2-ethanediamine; N-(2-aminoethyl)-N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine		C₁₀H₁₂ClF₃N₂	详情	详情
(VII)	33850	N-[2-[4-chloro(2,2,2-trifluoroethyl)anilino]ethyl]benzamide		C₁₇H₁₆ClF₃N₂O	详情	详情
(VIII)	33851	7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine		C₁₇H₁₄ClF₃N₂	详情	详情
(C)	10151	Ethyleneimine; Aziridine; Azirane	151-56-4	C₂H₅N	详情	详情

Extended Information