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【结 构 式】 
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【分子编号】35131 【品名】2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride 【CA登记号】89-75-8 |
【 分 子 式 】C7H3Cl3O 【 分 子 量 】209.45832 【元素组成】C 40.14% H 1.44% Cl 50.78% O 7.64% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Similarly, amide (IX) was prepared by acylation of (I) with 2,4-dichlorobenzoyl chloride (VIII) using the same method as in Scheme 22470201a.
| 【1】 Mori, H.; Ogawa, T.; Yamazaki, S.; Satoh, H.; Kitaguchi, H.; Nishikawa, N.; Xu, H.; Izushi, T. (Fuji Photo Film Co., Ltd.); Bisazo cpds.. EP 0747449; US 5717080; WO 9523189 . |
| 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) | 58749 | sodium 5-amino-4-hydroxy-7-sulfo-2-naphthalenesulfonate | C10H8NNaO7S2 | 详情 | 详情 | |
| (VIII) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (IX) | 58755 | disodium 4-[(2,4-dichlorobenzoyl)amino]-5-hydroxy-2,7-naphthalenedisulfonate | C17H9Cl2NNa2O8S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)2,4-Dichlorobenzoic acid (V) was converted to acid chloride (VI) using SOCl2. Further Friedel-Crafts condensation of (VI) with toluene in the presence of AlCl3 produced benzophenone (VII). Benzylic bromination of (VII) with N-bromosuccinimide gave bromide (VIII). Finally, displacement of the bromine of (VIII) by means of amine (IV) furnished the title compound.
| 【1】 Zhou, Y.; Zhang, W.; Li, K.; Jiang, Y.; Li, Y.; Wang, X.; The synthesis and antifungal activity of the substituted naphthalenemethanamines. Chin Journal of Medicinal Chemistry 1999, 9, 7, 7. |
| 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) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (V) | 33443 | 2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (VI) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (VII) | 35132 | (2,4-dichlorophenyl)(4-methylphenyl)methanone | C14H10Cl2O | 详情 | 详情 | |
| (VIII) | 35133 | [4-(bromomethyl)phenyl](2,4-dichlorophenyl)methanone | C14H9BrCl2O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Acylation of 2,4-dimethylimidazole (I) with 2,4-dichlorobenzoyl chloride (II) in the presence of diisopropylethylamine, followed by acidic hydrolysis, provides the 2-imidazolyl acetophenone (III). Subsequent condensation of (III) with dimethylformamide dimethylacetal gives rise to the enaminone (IV)
| 【1】 Brown, S.P.; Goff, D.; Ring, D.B.; Harrison, S.D.; Subramanian, S.; Nuss, J.M.; Boyce, R.S.; Johnson, K.; Pfister, K.B.; Ramurthy, S.; Renhowe, P.A.; Seely, L.; Wagman, A.S.; Zhou, X.A. (Chiron Corp.); Inhibitors of glycogen synthase kinase 3. EP 1087963; US 6417185; WO 9965897 . |
| 【2】 Ring, D.B.; Harrison, S.D.; Nuss, J.M.; Boyce, R.S.; Johnson, K.; Pfister, K.B.; Ramurthy, S.; Seely, L.; Wagman, A.S.; Desai, M.; Levine, B.H. (Chiron Corp.); Inhibitors of glycogen synthase kinase 3. WO 0220495 . |
| 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) | 20613 | 2,4-dimethyl-1H-imidazole | 930-62-1 | C5H8N2 | 详情 | 详情 |
| (II) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (III) | 60241 | 1-(2,4-dichlorophenyl)-2-(4-methyl-1H-imidazol-2-yl)-1-ethanone | C12H10Cl2N2O | 详情 | 详情 | |
| (IV) | 60242 | 1-(2,4-dichlorophenyl)-3-(dimethylamino)-2-(4-methyl-1H-imidazol-2-yl)-2-propen-1-one | C15H15Cl2N3O | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)Acylation of L-phenylalanine tert-butyl ester (I) with 2,4-dichlorobenzoyl chloride (II) provides the corresponding amide (III). This is then N-alkylated with 3-nitrobenzyl bromide (IV) in the presence of NaH to yield (V). The tert-butyl ester group of (V) is finally cleaved with trifluoroacetic acid to furnish the target carboxylic acid. (1-3)
| 【1】 Chan, L.; Reddy, J.; Proulx, M.; Das, S.K.; Pereira, O.; Wang, W.; Siddiqui, A.; Yannopoulos, C.G.; Poisson, C.; Turcotte, N.; Drouin, A.; Alaoui-Ismaili, M.H.; Bethell, R.; Hamel, M.; L'Heureux, L.; Bilimoria, D.; Nguyen-Ba, N.; Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase. J Med Chem 2003, 46, 8, 1283. |
| 【2】 Proulx, M.; Chan, L.; Reddy, T.J.; Das, S.K.; Pereira, O.Z.; Identification of a novel class of inhibitors of hepatitis C NS5B polymerase. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 40. |
| 【3】 Pereira, O.Z.; Wang, W.; Siddiqui, M.A.; Bedard, J.; Nguyen Ba, N.; Chan, C.K.L.; Das, S.K.; Shuttleworth, S. (Shire BioChem Inc.); Cpds. and methods for the treatment or prevention of flavivirus infections. US 2003229053; WO 02100846 . |
| 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) | 60837 | tert-butyl (2S)-2-amino-3-phenylpropanoate | C13H19NO2 | 详情 | 详情 | |
| (II) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (III) | 64057 | 1,1-dimethylethyl 2-{[(2,4-dichlorophenyl)carbonyl]amino}-3-phenylpropanoate | C20H21Cl2NO3 | 详情 | 详情 | |
| (IV) | 19636 | 1-(bromomethyl)-3-nitrobenzene | 3958-57-4 | C7H6BrNO2 | 详情 | 详情 |
| (V) | 64058 | 1,1-dimethylethyl 2-{[(2,4-dichlorophenyl)carbonyl][(3-nitrophenyl)methyl]amino}-3-phenylpropanoate | C27H26Cl2N2O5 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The title N-acyl sulfonamide is prepared by condensation of 4-chlorophenylsufonamide (I) with 2,4-dichlorobenzoyl chloride (II) in the presence of K2CO3.
| 【1】 Shih, C.; Grossman, C.S.; Lobb, K.L.; Corbett, T.H.; Hipskind, P.A.; Lin, H.-S. (Eli Lilly and Company); Benzoylsulfonamides and sulfonylbenzamidines for use as antitumour agents. WO 0298848 . |