2,3-dichlorophenylamine -Drug Synthesis Database

【结构式】

【分子编号】28562

【品名】2,3-dichlorophenylamine

【CA登记号】608-27-5

【分子式】C₆H₅Cl₂N

【分子量】162.01784

【元素组成】C 44.48% H 3.11% Cl 43.76% N 8.65%

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：(IX)

The diazotation of 2,3-dichloroaniline (IX) with NaNO2 and HCl gives the corresponding diazonium chloride (X), which by a Sandmeyer reaction with CuCN yields 2,3-dichlorophenyl cyanide (XI). The Grignard reaction of (XI) with methylmagnesium bromide (A) in ether affords 2,3-dichloroacetophenone (XII), which by a Willgerodt reaction with S and morpholine is converted into 2,3-dichlorophenylacetic acid (XIII). The reaction of (XIII) with oxalyl chloride (B) in carbon tetrachloride affords the corresponding acyl chloride (XIV), which is cyclized with ethylene (C) by means of AlCl3 in methylene chloride yielding 7,8-dichloro-2-tetralone (XV). The reaction of (XV) with sodium azide in CHCl3 by means of H2SO4 gives 8,9-dichloro-2-benzazepin-3-one (XVI), which is finally reduced with diborane in THF.

参考文献中间体

合成目标

【1】 Molloy, B.B.; Chlorinated tetrahydro-2-benzazepines, N-methyl transferase inhibitors. CA 1119592 .
【2】 Serradell, M.N.; Castaner, J.; LY-134046. Drugs Fut 1984, 9, 4, 268.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(A)	33623	bromo(methyl)magnesium	75-16-1	CH₃BrMg	详情	详情
(IX)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(X)	34165	2,3-dichlorobenzenediazonium chloride		C₆H₃Cl₃N₂	详情	详情
(XI)	30204	2,3-dichlorobenzonitrile	6574-97-6	C₇H₃Cl₂N	详情	详情
(XII)	34166	1-(2,3-dichlorophenyl)-1-ethanone		C₈H₆Cl₂O	详情	详情
(XIII)	34167	2-(2,3-dichlorophenyl)acetic acid		C₈H₆Cl₂O₂	详情	详情
(XIV)	34168	2-(2,3-dichlorophenyl)acetyl chloride		C₈H₅Cl₃O	详情	详情
(XV)	34169	7,8-dichloro-3,4-dihydro-2(1H)-naphthalenone		C₁₀H₈Cl₂O	详情	详情
(XVI)	34170	8,9-dichloro-1,2,4,5-tetrahydro-3H-2-benzazepin-3-one		C₁₀H₉Cl₂NO	详情	详情
(C)	28363	ethylene	9002-88-4	C₂H₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Hydrogenation of 2,3-dichloronitrobenzene (I) with H2 over Ra-Ni in methanol gives 2,3-dichloroaniline (II), which is diazotized with NaNO2 and HCl and treated with CuCN to yield 2,3-dichlorobenzonitrile (III). Hydrolysis of the nitrile (III) with NaOH in refluxing methanol/water affords 2,3-dichlorobenzoic acid (IV), which is treated with hot SOCl2 to provide the corresponding acyl chloride (V). Reaction of (V) with CuCN and KI in refluxing chlorobenzene gives 2,3-dichlorobenzoyl cyanide (VI), which is condensed with aminoguanidine (VII) by means of H2SO4/TsOH in hot toluene to yield 2,3-dichlorobenzoyl cyanide amidinohydrazone (VIII). Finally, this compound is cyclized by treatment with NaOMe in refluxing methanol.

参考文献中间体

合成目标

【1】 Srivastava, A.R.; Sasikumar, T.M.; Radhakrishnan, T.V. (RPG Life Sciences Ltd); A process for the preparation of 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, commonly known as lamotrigine. WO 0149669 .

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)	52655	2,3-Dichloronitrobenzene; 1,2-Dichloro-3-Nitrobenzene; Nitro-o-dichlorobenzene	3209-22-1	C₆H₃Cl₂NO₂	详情	详情
(II)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(III)	30204	2,3-dichlorobenzonitrile	6574-97-6	C₇H₃Cl₂N	详情	详情
(IV)	24007	2,3-dichlorobenzoic acid	50-45-3	C₇H₄Cl₂O₂	详情	详情
(V)	24008	2,3-dichlorobenzoyl chloride	2905-60-4	C₇H₃Cl₃O	详情	详情
(VI)	24009	2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide	77668-42-9	C₈H₃Cl₂NO	详情	详情
(VII)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情
(VIII)	52654	2-[cyano(phenyl)methylidene]-1-hydrazinecarboximidamide		C₉H₉N₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Dichlorophenylpiperazine (III) was prepared from aniline (I) by dehydrative cyclization with diethanolamine (II) in the presence of P2O5 and Et3N-HCl at 200 C. Alkylation of piperazine (III) with N-(4-bromobutyl) phthalimide (IV) gave (V), and subsequent hydrazinolysis of the phthalimide provided the (4-aminobutyl)piperazine (VI). Finally, condensation of (VI) with fluorene-2-carboxylic acid (VII) yielded the target amide.

参考文献中间体

合成目标

【1】 Yuan, J.; Chen, X.; Brodbeck, R.; Primus, R.; Braun, J.; Wasley, W.F.; Thurkauf, A.; NGB 2904 and NGB 2849: Two highly selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1998, 8, 19, 2715.
【2】 Yuan, J.; Chen, X. (Neurogen Corp.); Novel N-aminoalkylfluorenecarboxamides; a new class of dopamine receptor subtype specific ligands. EP 0873329; JP 1998511114; US 5659033; WO 9710229 .

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)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(II)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情
(III)	13943	1-(2,3-Dichlorophenyl)piperazine	41202-77-1	C₁₀H₁₂Cl₂N₂	详情	详情
(IV)	17163	N-(4-Bromobutyl)phthalimide; 2-(4-Bromobutyl)-1H-isoindole-1,3(2H)-dione	5394-18-3	C₁₂H₁₂BrNO₂	详情	详情
(V)	28563	2-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₃Cl₂N₃O₂	详情	详情
(VI)	28564	4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butylamine		C₁₄H₂₁Cl₂N₃	详情	详情
(VII)	28566	9H-fluorene-2-carboxylic acid		C₁₄H₁₀O₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Dichlorophenylpiperazine (III) was prepared from aniline (I) by dehydrative cyclization with diethanolamine (II) in the presence of P2O5 and Et3N-HCl at 200 C. Alkylation of piperazine (III) with N-(4-bromobutyl) phthalimide (IV) gave (V), and subsequent hydrazinolysis of the phthalimide provided the (4-aminobutyl)piperazine (VI). Finally, condensation of (VI) with biphenylene-2-carboxylic acid (VII) yielded the target amide.

参考文献中间体

合成目标

【1】 Yuan, J.; Chen, X.; Brodbeck, R.; Primus, R.; Braun, J.; Wasley, W.F.; Thurkauf, A.; NGB 2904 and NGB 2849: Two highly selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1998, 8, 19, 2715.

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)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(II)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情
(III)	23943	2-methoxyisonicotinonitrile		C₇H₆N₂O	详情	详情
(IV)	17163	N-(4-Bromobutyl)phthalimide; 2-(4-Bromobutyl)-1H-isoindole-1,3(2H)-dione	5394-18-3	C₁₂H₁₂BrNO₂	详情	详情
(V)	28563	2-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₃Cl₂N₃O₂	详情	详情
(VI)	28564	4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butylamine		C₁₄H₂₁Cl₂N₃	详情	详情
(VII)	28565	2-biphenylenecarboxylic acid		C₁₃H₈O₂	详情	详情

Extended Information