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【结 构 式】 
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【分子编号】30791 【品名】1-(4-chloro-1,2,5-thiadiazol-3-yl)-4-azatricyclo[2.2.1.0(2,6)]heptane 【CA登记号】 |
【 分 子 式 】C8H8ClN3S 【 分 子 量 】213.69044 【元素组成】C 44.97% H 3.77% Cl 16.59% N 19.66% S 15.01% |
合成路线1
该中间体在本合成路线中的序号：(IV)Reduction of cyanoazatricycloheptane (I) with diisobutylaluminum hydride produced aldehyde (II), which was treated with KCN and ammonia yielding aminonitrile (III). Cyclization of (III) with sulfur monochloride in DMF gave the 3-chloro-1,2,5-thiadiazole (IV). Displacement of the halogen atom of (IV) with sodium hydrogen sulfide, followed by alkylation with propyl bromide afforded the propyl thioether (V), which was oxidized to sulfone (VI) using oxone(R). The arylpropynol intermediate (IX) was prepared by coupling of 1-bromo-3,5-difluorobenzene (VII) with propargyl alcohol (VIII) in the presence of PdCl2(PPh3)2 and CuI. Reaction of sulfone (VI) with arylpropynol (IX) in the presence of NaH in THF provided the target ether (X). Finally, treatment of (X) with oxalic acid in acetone furnished the corresponding oxalate salt.
| 【1】 Jeppesen, L.; Olesen, P.H.; Hansen, L.; et al.; 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: Structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. J Med Chem 1999, 42, 11, 1999. |
| 【2】 Jeppesen, L.; Olesen, P.H.; Sauerberg, P. (Novo Nordisk A/S); Heterocyclic cpds. and their preparation and use. EP 0891363; JP 1999509864; US 5914338; WO 9736906 . |
| 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) | 30788 | 4-azatricyclo[2.2.1.0(2,6)]heptane-1-carbonitrile | C7H8N2 | 详情 | 详情 | |
| (II) | 30789 | 4-azatricyclo[2.2.1.0(2,6)]heptane-1-carbaldehyde | C7H9NO | 详情 | 详情 | |
| (III) | 30790 | 2-amino-2-(4-azatricyclo[2.2.1.0(2,6)]hept-1-yl)acetonitrile | C8H11N3 | 详情 | 详情 | |
| (IV) | 30791 | 1-(4-chloro-1,2,5-thiadiazol-3-yl)-4-azatricyclo[2.2.1.0(2,6)]heptane | C8H8ClN3S | 详情 | 详情 | |
| (V) | 30792 | 1-[4-(propylsulfanyl)-1,2,5-thiadiazol-3-yl]-4-azatricyclo[2.2.1.0(2,6)]heptane; 4-(4-azatricyclo[2.2.1.0(2,6)]hept-1-yl)-1,2,5-thiadiazol-3-yl propyl sulfide | C11H15N3S2 | 详情 | 详情 | |
| (VI) | 30793 | 4-(4-azatricyclo[2.2.1.0(2,6)]hept-1-yl)-1,2,5-thiadiazol-3-yl propyl sulfone; 1-[4-(propylsulfonyl)-1,2,5-thiadiazol-3-yl]-4-azatricyclo[2.2.1.0(2,6)]heptane | C11H15N3O2S2 | 详情 | 详情 | |
| (VII) | 30794 | 1-bromo-3,5-difluorobenzene | 461-96-1 | C6H3BrF2 | 详情 | 详情 |
| (VIII) | 16664 | Propargyl Alcohol; 2-propyn-1-ol | 107-19-7 | C3H4O | 详情 | 详情 |
| (IX) | 30795 | 3-(3,5-difluorophenyl)-2-propyn-1-ol | C9H6F2O | 详情 | 详情 | |
| (X) | 30796 | 4-(4-azatricyclo[2.2.1.0(2,6)]hept-1-yl)-1,2,5-thiadiazol-3-yl 3-(3,5-difluorophenyl)-2-propynyl ether; 1-(4-[[3-(3,5-difluorophenyl)-2-propynyl]oxy]-1,2,5-thiadiazol-3-yl)-4-azatricyclo[2.2.1.0(2,6)]heptane | C17H13F2N3OS | 详情 | 详情 |