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【结 构 式】 
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【分子编号】27360 【品名】4-chlorobenzonitrile 【CA登记号】623-03-0 |
【 分 子 式 】C7H4ClN 【 分 子 量 】137.5682 【元素组成】C 61.12% H 2.93% Cl 25.77% N 10.18% |
合成路线1
该中间体在本合成路线中的序号：(VI)By cyclization of isoquinolinone (IV) with 4-chlorobenzonitrile (VI) by means of sodium ethoxide in refluxing ethanol.
| 【1】 Omodei-Sale, A.; Favara, D. (Lepetit SpA); Triazolo[5,1-a]isoquinoline deriv. DE 2942195; FR 2440369 . |
| 【2】 de Angelis, L.; Castaner, J.; Lotrifen. Drugs Fut 1985, 10, 10, 817. |
合成路线2
该中间体在本合成路线中的序号：(III)A scaleable process to produce vorozole has been reported: The reaction of 2,4-dichloronitrobenzene (I) with methylamine gives 5-chloro-N-methyl-2-nitroaniline (II), which is condensed with 4-chlorobenzonitrile (III) and oxidized with air to yield 4'-chloro-3-(methylamino)-4-nitrobenzophenone (IV). The hydrogenation of compound (IV), followed by cyclization by means of nitrous acid and reduction of the carbonyl group with NaBH4 affords the benzotriazole (V). Reaction of the OH group of (V) with SOCl2 provides the corresponding chloro derivative (VI), which is treated with acetohydrazide (VII) to give the racemic hydrazine derivative (VIII). Optical resolution of (VIII) by chiral chromatography yields the (S)-isomer (IX), which is finally cyclized with formamidine to afford vorozole.
| 【1】 De Knaep, A.G.M.; Vandendriessche, A.M.J.; Daemen, D.J.E.; et al.; Development summary towards a manufacturable process for R 83842 [(S)-6-[(4-chlorophenyl) (1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole]. Org Process Res Dev 2000, 4, 3, 162. |
| 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) | 21787 | 2,4-dichloro-1-nitrobenzene | 611-06-3 | C6H3Cl2NO2 | 详情 | 详情 |
| (II) | 46715 | 5-chloro-N-methyl-2-nitroaniline; N-(5-chloro-2-nitrophenyl)-N-methylamine | 35966-84-8 | C7H7ClN2O2 | 详情 | 详情 |
| (III) | 27360 | 4-chlorobenzonitrile | 623-03-0 | C7H4ClN | 详情 | 详情 |
| (IV) | 46716 | (4-chlorophenyl)[3-(methylamino)-4-nitrophenyl]methanone | C14H11ClN2O3 | 详情 | 详情 | |
| (V) | 14734 | (4-chlorophenyl)(1-methyl-1H-1,2,3-benzotriazol-6-yl)methanol | C14H12ClN3O | 详情 | 详情 | |
| (VI) | 14735 | 6-[chloro(4-chlorophenyl)methyl]-1-methyl-1H-1,2,3-benzotriazole | C14H11Cl2N3 | 详情 | 详情 | |
| (VII) | 29262 | acetohydrazide | 1068-57-1 | C2H6N2O | 详情 | 详情 |
| (VIII) | 46717 | 6-[(4-chlorophenyl)(hydrazino)methyl]-1-methyl-1H-1,2,3-benzotriazole | C14H14ClN5 | 详情 | 详情 | |
| (IX) | 46718 | 6-[(S)-(4-chlorophenyl)(hydrazino)methyl]-1-methyl-1H-1,2,3-benzotriazole | C14H14ClN5 | 详情 | 详情 | |
| (X) | 15369 | Iminoformamide; Methanimidamide | 463-52-5 | CH4N2 | 详情 | 详情 |