【结 构 式】 |
【分子编号】60375 【品名】2-[6-(1-pyrrolidinyl)-3-pyridinyl]acetonitrile 【CA登记号】 |
【 分 子 式 】C11H13N3 【 分 子 量 】187.24444 【元素组成】C 70.56% H 7% N 22.44% |
合成路线1
该中间体在本合成路线中的序号:(VII)6-Chloronicotinic acid (I) is converted to the corresponding acid chloride (II) employing either SOCl2 or PCl5/POCl3. Treatment of acid chloride (II) with EtOH and Et3N, followed by reduction of the resultant ethyl ester with LiAlH4, furnishes 6-chloro-3-pyridylmethanol (III). Alcohol (III) is alternatively prepared by NaBH4 reduction of acid chloride (II). Chlorination of (III) by using SOCl2 gives the chloromethyl pyridine (IV), and further chloride displacement with KCN leads to nitrile (V). Substitution of the remaining chloride group of (V) upon heating with pyrrolidine (VI) furnishes the pyrrolidinyl pyridine (VII). Then hydrolysis of the nitrile function of (VII) under acidic conditions provides carboxylic acid (VIII). Bromination of 4-(methylsulfonyl)acetophenone (IX) in the presence of AlCl3 produces the phenacyl bromide (X). Finally, condensation between acid (VIII) and bromo ketone (X) under basic conditions gives rise to the title diaryl furanone
【1】 Almansa, C.; Alfon, J.; Cavalcanti, F.L.; Gomez, L.; Miralles, A.; Synthesis and SAR of 4-pyrrolidinylarylheterocycles as COX-2 selective inhibitors. Drugs Fut 2002, 27, Suppl. A. |
【2】 Almansa Rosales, C.; Gonzalez Gonzalez, C.; Torres Barreda, M.C. (J. Uriach & Cia., SA); Novel heterocyclic cpds. with anti-inflammatory activity. EP 1281709; ES 2166710; WO 0183475 . |
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) | 12996 | 6-Chloronicotinic acid | 5326-23-8 | C6H4ClNO2 | 详情 | 详情 |
(II) | 30256 | 6-chloronicotinoyl chloride | 58757-38-3 | C6H3Cl2NO | 详情 | 详情 |
(III) | 60372 | (6-chloro-3-pyridinyl)methanol | C6H6ClNO | 详情 | 详情 | |
(IV) | 60373 | 2-chloro-5-(chloromethyl)pyridine | C6H5Cl2N | 详情 | 详情 | |
(V) | 60374 | 2-(6-chloro-3-pyridinyl)acetonitrile | C7H5ClN2 | 详情 | 详情 | |
(VI) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
(VII) | 60375 | 2-[6-(1-pyrrolidinyl)-3-pyridinyl]acetonitrile | C11H13N3 | 详情 | 详情 | |
(VIII) | 60376 | 2-[6-(1-pyrrolidinyl)-3-pyridinyl]acetic acid | C11H14N2O2 | 详情 | 详情 | |
(IX) | 19263 | 1-[4-(methylsulfonyl)phenyl]-1-ethanone; 4-methylsulfonylacetophenone | 10297-73-1 | C9H10O3S | 详情 | 详情 |
(X) | 19264 | 2-bromo-1-[4-(methylsulfonyl)phenyl]-1-ethanone | C9H9BrO3S | 详情 | 详情 |