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【结 构 式】 
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【分子编号】10105 【品名】1-Bromonaphthalene 【CA登记号】90-11-9 |
【 分 子 式 】C10H7Br 【 分 子 量 】207.06958 【元素组成】C 58% H 3.41% Br 38.59% |
合成路线1
该中间体在本合成路线中的序号：(I)1) The Grignard reaction of 1-bromonaphthalene (I) with Mg in THF and then with [14C]-labeled CO2 gives the corresponding 1-naphthoic acid (II), which by reaction with SO2Cl2 and then with methylamine yields [14C]-N-methyl-1-naphthalenecarboxamide (III). The reduction of (III) with LiAlH4 in refluxing THF affords the corresponding amine (IV). Finally, this compound is condensed with 1-bromo-6,6-dimethylhept-2-en-4-yne (V) by means of Na2CO3 in DMF, and treated with ethanolic HCl.
| 【1】 Andres, H.; Carbon-14 labelling of terbinafine, an antimycotic agent. J Label Compd Radiopharm 1989, 27, 11, 1307. |
| 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) | 10105 | 1-Bromonaphthalene | 90-11-9 | C10H7Br | 详情 | 详情 |
| (II) | 10106 | 1-Naphthoic acid | 86-55-5 | C11H8O2 | 详情 | 详情 |
| (II) | 44581 | 1-naphthoic acid | C11H8O2 | 详情 | 详情 | |
| (III) | 10107 | N-Methyl-1-naphthamide | 3400-33-7 | C12H11NO | 详情 | 详情 |
| (III) | 44582 | N-methyl-1-naphthamide | C12H11NO | 详情 | 详情 | |
| (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 |
| (IV) | 44583 | N-methyl(1-naphthyl)methanamine; N-methyl-N-(1-naphthylmethyl)amine | C12H13N | 详情 | 详情 | |
| (V) | 10109 | (E)-1-Bromo-6,6-dimethyl-2-hepten-4-yne | 78629-21-7 | C9H13Br | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)Oxidation of (4-cyclopropyl-1-naphthyl)methanol (XI) by means of MnO2 in CH2Cl2 yields 4-cyclopropyl-1-naphthaldehyde (XII), which is then treated with NH2OH·HCl or (NH2OH)2SO4 in the presence of NaOMe (generated from Na in MeOH) to give 4-cyclopropyl-1-naphthaldehyde oxime (XIII). Bromination of oxime (XIII) with NBS in acetonitrile provides the corresponding oximidoyl bromide (XIV), which is finally treated with CS(NH2)2 in the presence of Et3N in THF (I) .
Chlorination of oxime (XIII) using 1,3-dichloro-5,5-dimethylhydantoin (DDH) or trichloroisocyanuric acid (TCCA) in acetonitrile affords 4-cyclopropyl-N-hydroxynaphthalene-1-carboximidoyl chloride (XV), which is then treated with CS(NH2)2 or CH3CSNH2 in the presence of Et3N in THF .
Coupling of 1-bromonaphthalene (XVI) with cyclopropylmagnesium bromide (XVII) in the presence of NiCl2(dppp) in THF gives 1-cyclopropylnaphthalene (XVIII), which is then nitrated with NaNO2 at 0 °C to produce 1-cyclopropyl-4-nitronaphthalene (XIX). Reduction of the nitronaphthalene derivative (XIX) by means of H2 over Pd/C in EtOH yields 4-cyclopropyl-1-naphthylamine (XX), which is finally treated with CSCl2 and DIEA in CH2Cl2 at 0 °C .
| 【1】 Miner, J., Quart, B.D., Girardet, J.-L. (Ardea Biosciences, Inc.). Treatment of gout. WO 201116852. |
| 【2】 Quart, B.D., Girardet, J.-L., Gunic, E., Yeh, L.-T. (Ardea Biosciences, Inc.).Novel compounds and composition and methods of use. CA 2706858, CN 01918377, EP 2217577, JP 2011504935, KR 2010085195, US 2009197825, US 2011268801, WO 009070740. |
| 【3】 Zamansky, I., Galvin, G., Girardet, J.-L. (Ardea Biosciences, Inc.). Polymorphic, crystalline and mesophase forms of sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate, and uses thereof. WO 2011085009. |
| 【4】 Liu, X., Hong, D., Wu, X. (Taizhou Hwasun Pharm. & Chem. Co., Ltd.). Method for preparing 4-cyclopropyl-1-isothiocyanonaphthalene and intermediate 4-cyclopropyl-1-naphthaldehyde oxime/halide. CN 102040546. |
| 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) | 68901 | 4-cyclopropyl-1-naphthyl isothiocyanate | 878671-95-5 | C14H11NS | 详情 | 详情 |
| (XI) | 68910 | (4-cyclopropyl-1-naphthyl)methanol | C14H14O | 详情 | 详情 | |
| (XII) | 68911 | 4-cyclopropyl-1-naphthaldehyde | C14H12O | 详情 | 详情 | |
| (XIII) | 68912 | (Z)-4-cyclopropyl-1-naphthaldehyde oxime;4-cyclopropyl-1-naphthaldehyde oxime | C14H13NO | 详情 | 详情 | |
| (XIV) | 68914 | (E)-4-cyclopropyl-N-hydroxy-1-naphthimidoyl bromide | C14H12BrNO | 详情 | 详情 | |
| (XV) | 68913 | 4-cyclopropyl-N-hydroxynaphthalene-1-carboximidoyl chloride;(E)-4-cyclopropyl-N-hydroxy-1-naphthimidoyl chloride | C14H12ClNO | 详情 | 详情 | |
| (XVI) | 10105 | 1-Bromonaphthalene | 90-11-9 | C10H7Br | 详情 | 详情 |
| (XVII) | 12450 | Bromo(cyclopropyl)magnesium;cyclopropylmagnesium bromide;cyclopropylmagnesiumbromide | 23719-80-4 | C3H5BrMg | 详情 | 详情 |
| (XVIII) | 68915 | 1-cyclopropylnaphthalene | 25033-19-6 | C13H12 | 详情 | 详情 |
| (XIX) | 68916 | 1-cyclopropyl-4-nitronaphthalene | C13H11NO2 | 详情 | 详情 | |
| (XX) | 68917 | 4-cyclopropyl-1-naphthylamine | 878671-94-4 | C13H13N | 详情 | 详情 |