|
【结 构 式】 
|
【分子编号】34058 【品名】2-(3-chlorophenyl)-3-oxo-3-(3-pyridinyl)propanenitrile 【CA登记号】 |
【 分 子 式 】C14H9ClN2O 【 分 子 量 】256.69104 【元素组成】C 65.51% H 3.53% Cl 13.81% N 10.91% O 6.23% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Condensation of ethyl nicotinate (XI) with 3-chlorophenylacetonitrile (XII) by means of sodium ethoxide in ethanol gives 2-(3-chlorophenyl)-3-oxo-3-(3-pyridyl)propionitrile (XIII), which by refluxing with concentrated HBr yields 2-(3-chlorophenyl)-1-(3-pyridyl)ethanone (XIV). The reduction of (XIV) with hydrazine hydrate and NaOH in diethylene glycol at 235-40 C affords 3-(2-phenylethyl) pyridine (XV), which is oxidized with H2O2 in hot acetic acid to provide the corresponding N-oxide (XVI). Reaction of (XVI) with NaCN and dimethyl sulfate in water affords the previously described 3-(2-phenylethyl)pyridine-2-carbonitrile (V), which can be worked up as previously described or cyclized with polyphosphoric acid (PPA) at 180 C to give 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (XVII). The condensation of (XVII) with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF yields the corresponding carbinol (XVIII), which is dehydrated with PPA at 170 C to afford the previously reported 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII).
| 【1】 Castaner, J.; Leeson, P.; Graul, A.; Desloratadine. Drugs Fut 2000, 25, 4, 339. |
| 【2】 Villani, F.J. (Schering Corp.); Novel aza-dibenzo[a,d]cycloheptene derivatives. US 3326924 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 20644 | 3-(3-chlorophenethyl)-2-pyridinecarbonitrile | C14H11ClN2 | 详情 | 详情 | |
| (VI) | 20645 | chloro(1-methyl-4-piperidinyl)magnesium | C6H12ClMgN | 详情 | 详情 | |
| (VIII) | 20647 | 8-chloro-11-(1-methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | 38092-89-6 | C20H21ClN2 | 详情 | 详情 |
| (XI) | 23226 | ethyl nicotinate | 614-18-6 | C8H9NO2 | 详情 | 详情 |
| (XII) | 34057 | 2-(3-chlorophenyl)acetonitrile; 3-chlorophenylacetonitrile | 1529-41-5 | C8H6ClN | 详情 | 详情 |
| (XIII) | 34058 | 2-(3-chlorophenyl)-3-oxo-3-(3-pyridinyl)propanenitrile | C14H9ClN2O | 详情 | 详情 | |
| (XIV) | 34059 | 2-(3-chlorophenyl)-1-(3-pyridinyl)-1-ethanone | C13H10ClNO | 详情 | 详情 | |
| (XV) | 34060 | 3-(3-chlorophenethyl)pyridine | C13H12ClN | 详情 | 详情 | |
| (XVI) | 34061 | 3-(3-chlorophenethyl)-1-pyridiniumolate | C13H12ClNO | 详情 | 详情 | |
| (XVII) | 16504 | 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one; 8-Chloro-10,11-dihydro-4-aza-5H-dibenzo[a,d]cycloheptan-5-one | 31251-41-9 | C14H10ClNO | 详情 | 详情 |
| (XVIII) | 23553 | 8-chloro-11-(1-methyl-4-piperidinyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol | C20H23ClN2O | 详情 | 详情 |