【结 构 式】 |
【分子编号】30204 【品名】2,3-dichlorobenzonitrile 【CA登记号】6574-97-6 |
【 分 子 式 】C7H3Cl2N 【 分 子 量 】172.01296 【元素组成】C 48.88% H 1.76% Cl 41.22% N 8.14% |
合成路线1
该中间体在本合成路线中的序号:(XI)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.
【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:(III)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.
【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:(II)The condensation of 2-methylpyridine (I) with 2,3-dichlorobenzonitrile (II) by means of BuLi and diisopropylamine in THF gives the vinyl derivative (III), which is cyclized by heating at 200 C.
【1】 Mettey, Y.; Vierfond, J.-M.; Benzo[c]quinoliziums: A new family of inhibitors for protein kinase CK II. Bioorg Med Chem Lett 1997, 7, 8, 961. |
【2】 Becq, F.; Mettey, Y.; Vierfond, J.-M.; Verrier, B.; Gola, M. (CNRS (Centre National de la Recherche Scientifique)); CFTR channel activator cpds. and pharmaceutical compsns. containing same. EP 0937044; WO 9805642 . |