【结 构 式】 |
【分子编号】33125 【品名】methyl 3-(5-methoxy-3-nitro-3,4-dihydro-2H-chromen-3-yl)propanoate 【CA登记号】 |
【 分 子 式 】C14H17NO6 【 分 子 量 】295.29212 【元素组成】C 56.94% H 5.8% N 4.74% O 32.51% |
合成路线1
该中间体在本合成路线中的序号:(III)The condensation of 5-methoxy-3-nitro-3,4-dihydro-2H-1-benzopyran (I) with methyl acrylate (II) by means of benzyltrimethylammonium methoxide in methanol gives the propionic ester (III), which is submitted to a reductive cyclization with H2 over RaNi in methanol yielding the racemic spiro compound (IV). Optical resolution of (IV) by means of (+)-1,1'-dinaphthyl-2,2'-diyl hydrogen phosphate [(+)-BNP] in methanol/dichloromethane affords (+)(R)-(V), which is finally condensed with 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione (VI) by means of triethylamine (TEA) in hot DMF.
【1】 Comoy, C.; et al.; 3-Amino-3,4-dihydro-2H-1-benzopyran derivatives as 5-HT1A receptor ligands and potential anxiolytic agents. 2. Synthesis and quantitative structure-activity relationship studies of spiro[pyrrolidine- and piperidine-2, 3'(2'H)-benzopyrans]. J Med Chem 1996, 39, 21, 4285. |
【2】 Guillaumet, G.; Podona, T.; Adam, G.; Guardiola, B.; Renard, P. (ADIR et Cie.); 3-Aminochromane spiro derivs., processes for their preparation and pharmaceutical compsns. containing them. EP 0564358; FR 2689509; JP 1994287190; JP 1995084471; US 5376661; US 5397783 . |
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) | 33124 | methyl 3-nitro-3,4-dihydro-2H-chromen-5-yl ether; 5-methoxy-3-nitrochromane | C10H11NO4 | 详情 | 详情 | |
(II) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
(III) | 33125 | methyl 3-(5-methoxy-3-nitro-3,4-dihydro-2H-chromen-3-yl)propanoate | C14H17NO6 | 详情 | 详情 | |
(IV) | 33126 | 5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine] | C13H17NO2 | 详情 | 详情 | |
(V) | 33127 | (R)-5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine] | C13H17NO2 | 详情 | 详情 | |
(VI) | 29455 | 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione | C13H20BrNO2 | 详情 | 详情 |