|
【结 构 式】 
|
【分子编号】63299 【品名】benzyl [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether; 4-({2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazol-1-yl}methyl)pyridine 【CA登记号】 |
【 分 子 式 】C20H23N3O 【 分 子 量 】321.42224 【元素组成】C 74.74% H 7.21% N 13.07% O 4.98% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Alkylation of 2-(benzyloxymethyl)-4-isopropyl-1H-imidazole (VI) with 4-(chloromethyl)pyridine (X) by means of NaOH in toluene gives 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI), which is then condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) - obtained by reaction of bis(3,5-dichlorophenyl)-disulfide (VIII) first with chlorine gas in CCl4 or toluene and then dried nitrogen gas - by means of triethylamine in toluene/water to afford 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XI). Debenzylation of compound (XI) by means of hot aqueous HCl provides the hydroxymethyl derivative (XII), which is finally esterified with chlorosulfonyl isocyanate in ethyl acetate.
| 【1】 Sorbera, L.A.; Castañer, J.; Bayes, M.; Capravirine. Drugs Fut 2003, 28, 12, 1149. |
| 【2】 Kabaki, M.; Hajima, M.; Hozumi, Y. (Shionogi & Co. Ltd.); Process for producing imidazole derivs.. EP 0949249; US 6057448; WO 9829395 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 35841 | benzyl (4-isopropyl-1H-imidazol-2-yl)methyl ether; 2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazole | C14H18N2O | 详情 | 详情 | |
| (X) | 10844 | 4-(Chloromethyl)pyridine | 10445-91-7 | C6H6ClN | 详情 | 详情 |
| (XI) | 35845 | 4-([2-[(benzyloxy)methyl]-5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1H-imidazol-1-yl]methyl)pyridine; benzyl [5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether | C26H25Cl2N3OS | 详情 | 详情 | |
| (XII) | 35846 | [5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methanol | C19H19Cl2N3OS | 详情 | 详情 | |
| (XV) | 35843 | bis(3,5-dichlorophenyl) disulfide; 1,3-dichloro-5-[(3,5-dichlorophenyl)disulfanyl]benzene | 137897-99-5 | C12H6Cl4S2 | 详情 | 详情 |
| (XVI) | 63299 | benzyl [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether; 4-({2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazol-1-yl}methyl)pyridine | C20H23N3O | 详情 | 详情 | |
| (XVII) | 63000 | methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate | C29H28Br2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)Debenzylation of 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI) with hot aqueous HCl gives the hydroxymethyl derivative (XVIII), which is condensed with chlorosulfonyl isocyanate in ethyl acetate to yield carbamic acid 1-(4-pyridylmethyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIX). Finally, this compound is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in DMF/toluene.
| 【1】 Sorbera, L.A.; Castañer, J.; Bayes, M.; Capravirine. Drugs Fut 2003, 28, 12, 1149. |
| 【2】 Kabaki, M.; Hajima, M.; Hozumi, Y. (Shionogi & Co. Ltd.); Process for producing imidazole derivs.. EP 0949249; US 6057448; WO 9829395 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 63299 | benzyl [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether; 4-({2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazol-1-yl}methyl)pyridine | C20H23N3O | 详情 | 详情 | |
| (XVII) | 63000 | methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate | C29H28Br2O3 | 详情 | 详情 | |
| (XVIII) | 63301 | [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methanol | C13H17N3O | 详情 | 详情 | |
| (XIX) | 63302 | [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl carbamate | C14H18N4O2 | 详情 | 详情 |