【结 构 式】 |
【分子编号】63508 【品名】11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carboxylic acid 【CA登记号】 |
【 分 子 式 】C29H38N2O4S 【 分 子 量 】510.6978 【元素组成】C 68.2% H 7.5% N 5.49% O 12.53% S 6.28% |
合成路线1
该中间体在本合成路线中的序号:(XIII)Alkylation of the spiro lactone (VI) with dibromide (VII) in the presence of lithium hexamethyldisilazide gives rise to the tricyclic spiro compound (VIII). After acidic Boc group cleavage in (VIII), the resultant secondary amine (IX) is reductively alkylated with aldehyde (V) to produce (X) as a diastereomeric mixture. Partial reduction of lactone (X) with DIBAL provides lactol (XI), which is further converted to nitrile (XII) upon treatment with cyanotrimethylsilane and boron trifluoride. Acidic hydrolysis of nitrile (XII), followed by esterification of the resultant carboxylic acid (XIII) furnishes the methyl ester (XIV)
【1】 Pyrrolidine antagonists of the CCR3 chemokine receptor. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 250. |
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) | 63500 | 1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinecarbaldehyde | C16H17NOS | 详情 | 详情 | |
(VI) | 63501 | 1,1-dimethylethyl 2-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate | C13H21NO4 | 详情 | 详情 | |
(VII) | 63502 | 1-bromo-2-[(2-bromoethyl)oxy]ethane; bis(2-bromoethyl) ether | 5414-19-7 | C4H8Br2O | 详情 | 详情 |
(VIII) | 63503 | 1,1-dimethylethyl 15-oxo-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-11-carboxylate | C17H27NO5 | 详情 | 详情 | |
(IX) | 63504 | 3,14-dioxa-11-azadispiro[5.1.5.2]pentadecan-15-one | C12H19NO3 | 详情 | 详情 | |
(X) | 63505 | 11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecan-15-one | C28H36N2O3S | 详情 | 详情 | |
(XI) | 63506 | 11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecan-15-ol | C28H38N2O3S | 详情 | 详情 | |
(XII) | 63507 | 11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carbonitrile | C29H37N3O2S | 详情 | 详情 | |
(XIII) | 63508 | 11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carboxylic acid | C29H38N2O4S | 详情 | 详情 | |
(XIV) | 63509 | methyl 11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carboxylate | C30H40N2O4S | 详情 | 详情 |