11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carbonitrile -Drug Synthesis Database

【结构式】

【分子编号】63507

【品名】11-{[1-(phenylmethyl)-4-(3-thiophenyl)-3-pyrrolidinyl]methyl}-3,14-dioxa-11-azadispiro[5.1.5.2]pentadecane-15-carbonitrile

【CA登记号】

【分子式】C₂₉H₃₇N₃O₂S

【分子量】491.6978

【元素组成】C 70.84% H 7.58% N 8.55% O 6.51% S 6.52%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XII)

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)

参考文献中间体

合成目标

【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

Extended Information