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【结 构 式】 
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【分子编号】39966 【品名】2-(chloromethoxy)ethyl benzoate 【CA登记号】 |
【 分 子 式 】C10H11ClO3 【 分 子 量 】214.64824 【元素组成】C 55.96% H 5.17% Cl 16.52% O 22.36% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of benzonitrile (I) with refluxing ethylene glycol (II) gives ethylene glycol monobenzoate (III), which is chloromethylated with formaldehyde and dry HCl in CH2Cl2 affording 1-benzoyloxy-2-chloromethoxyethane (IV). The condensation of (IV) with 2,6-dichloropurine (V) by means of triethylamine in DMF yields 2,6-dichloro-9-(2-benzoyloxyethoxymethyl)purine (VI), which is aminated and debenzoylated by treatment with NH3 in methanol at 95 C in a pressure vessel giving 2-chloro-9-(2-hydroxyethoxymethyl)adenine (VII). The Sandmeyer reaction of (VII) with NaNO2 in acetic acid affords 2-chloro-9-(2-hydroxyethoxymethyl)hypoxanthine (VIII), which is finally amonolyzed with ammonia in methanol at 125 C in a pressure vessel.
| 【1】 Schaeffer, H.J.; et al.; 9-(2-Hydroxyethoxy)guanine activity aganist viruses of the herpes group. Nature 1978, 272, 583-585. |
| 【2】 Castaner, J.; Hillier, K.; Acycloguanosine. Drugs Fut 1978, 3, 11, 788. |
| 【3】 Schaeffer, H.J. (Glaxo Wellcome plc); Purine derivs.. US 4294831 . |
| 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) | 25904 | benzonitrile | 100-47-0 | C7H5N | 详情 | 详情 |
| (II) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (III) | 39965 | 2-hydroxyethyl benzoate | C9H10O3 | 详情 | 详情 | |
| (IV) | 39966 | 2-(chloromethoxy)ethyl benzoate | C10H11ClO3 | 详情 | 详情 | |
| (V) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (VI) | 39967 | 2-[(2,6-dichloro-9H-purin-9-yl)methoxy]ethyl benzoate | C15H12Cl2N4O3 | 详情 | 详情 | |
| (VII) | 39968 | 2-[(6-amino-2-chloro-9H-purin-9-yl)methoxy]-1-ethanol | C8H10ClN5O2 | 详情 | 详情 | |
| (VIII) | 39969 | 2-chloro-9-[(2-hydroxyethoxy)methyl]-9H-purin-6-ol | C8H9ClN4O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The condensation of guanine (IX) with refluxing hexamethyldisilazane followed by reaction with 1-benzoyloxy-2-chloromethoxyethane (IV) by means of triethylamine in refluxing benzene gives 9-(2-benzoyloxyethoxymethyl)guanine (X), which is finally hydrolyzed with ammonia in methanol at 80 C in a pressure vessel.
| 【1】 Castaner, J.; Hillier, K.; Acycloguanosine. Drugs Fut 1978, 3, 11, 788. |
| 【2】 Schaeffer, H.J. (Glaxo Wellcome plc); Purine derivs.. US 4294831 . |