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【结 构 式】 
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【分子编号】29478 【品名】6-[4-(2-amino-2-methylpropyl)phenoxy]nicotinamide 【CA登记号】 |
【 分 子 式 】C16H19N3O2 【 分 子 量 】285.34588 【元素组成】C 67.35% H 6.71% N 14.73% O 11.21% |
合成路线1
该中间体在本合成路线中的序号：(VI)By condensation of substituted nicotinamide (VI) with the carbazolyoxymethyl-oxirane (XII) in hot methanol/water. The intermediates the nicotinamide (VI) and the oxirane (XII) have been obtained as follows: 1.- Nicotinamide (VI): The reaction of 4-hydroxybenzyl alcohol (I) with 2-nitropropane (II) by means of potassium tert-butoxide in hot diglyme gives 4-(2-methyl-2-nitropropyl)phenol (III), which is reduced to the corresponding amino derivative (IV) with H2 over Pd/C in methanol/ethanol/acetic acid. Finally, this compound is condensed with 6-chloronicotinamide (V) by means of K2CO3 in dimethylacetamide/isooctane. 2.- Oxirane (XII): The reaction of phenylhydrazine (VII) with cyclohexane-1,3-dione (VIII) by means of NaHCO3 in isopropanol/water gives the monohydrazone (IX), which is cyclized with hotpolyphosphoric acid yielding the 4-hydroxycarbazole (X). Finally, this compound is condensed with the glycidyl 3-nitrophenylsulfonate (XI) by means of K2CO3 in refluxing acetone.
| 【1】 Crowell, T.A.; Evrard, D.A.; Jones, C.D.; Muehl, B.S.; Rito, C.J.; Shuker, A.J.; Thorpe, A.J.; Thrasher, K.J. (Eli Lilly and Company); Carbazole analogues as selective B3 adrenergic agonists. EP 0827746; WO 9809625 . |
| 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) | 29474 | 4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol | 623-05-2 | C7H8O2 | 详情 | 详情 |
| (II) | 21819 | 2-nitropropane | 79-46-9 | C3H7NO2 | 详情 | 详情 |
| (III) | 29475 | 4-(2-methyl-2-nitropropyl)phenol | C10H13NO3 | 详情 | 详情 | |
| (IV) | 29476 | 4-(2-amino-2-methylpropyl)phenol | 51706-55-9 | C10H15NO | 详情 | 详情 |
| (V) | 29477 | 6-chloronicotinamide | 6271-78-9 | C6H5ClN2O | 详情 | 详情 |
| (VI) | 29478 | 6-[4-(2-amino-2-methylpropyl)phenoxy]nicotinamide | C16H19N3O2 | 详情 | 详情 | |
| (VII) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (VIII) | 11244 | 1,3-Cyclohexanedione | 504-02-9 | C6H8O2 | 详情 | 详情 |
| (IX) | 29479 | 3-hydroxy-2-cyclohexen-1-one N-phenylhydrazone | C12H14N2O | 详情 | 详情 | |
| (X) | 29480 | 4-Hydroxycarbazole; 9H-carbazol-4-ol | 52602-39-8 | C12H9NO | 详情 | 详情 |
| (XI) | 16259 | (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate | 115314-14-2 | C9H9NO6S | 详情 | 详情 |
| (XII) | 29481 | 9H-carbazol-4-yl (2S)oxiranylmethyl ether; 4-[(2S)oxiranylmethoxy]-9H-carbazole | C15H13NO2 | 详情 | 详情 |