5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine] -Drug Synthesis Database

【结构式】

【分子编号】33126

【品名】5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine]

【CA登记号】

【分子式】C₁₃H₁₇NO₂

【分子量】219.28352

【元素组成】C 71.21% H 7.81% N 6.39% O 14.59%

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：(IV)

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.

参考文献中间体

合成目标

【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

Extended Information