8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione -Drug Synthesis Database

【结构式】

【分子编号】29455

【品名】8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione

【CA登记号】

【分子式】C₁₃H₂₀BrNO₂

【分子量】302.21134

【元素组成】C 51.67% H 6.67% Br 26.44% N 4.63% O 10.59%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

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

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 8-methoxy-3,4-dihydro-2H-1-benzopyran-3-amine (I) with 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione (II) by means of KI and triethylamine in ot DMF gives the secondary amine (III), which is alkylated with propyliodide and K2CO3 in hot DMF affording the tertiary amine (IV). Finally, this compound is treated with BBr3 in refluxing dichloromethane.

参考文献中间体

合成目标

【1】 Viaud, M.-C.; Pfeiffer, B.; Guillaumet, G.; Renard, P.; Rettori, M.-C.; Boyé, S.; N,N-Disubstituted aminomethyl benzofuran derivatives: Synthesis and preliminary binding evaluation. Bioorg Med Chem 1999, 7, 2, 335.

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)	29454	8-methoxy-3,4-dihydro-2H-chromen-3-ylamine; 8-methoxy-3-chromanamine	112904-73-1	C₁₀H₁₃NO₂	详情	详情
(II)	29455	8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione		C₁₃H₂₀BrNO₂	详情	详情
(III)	29456	8-[4-[(8-methoxy-3,4-dihydro-2H-chromen-3-yl)amino]butyl]-8-azaspiro[4.5]decane-7,9-dione		C₂₃H₃₂N₂O₄	详情	详情
(IV)	29457	8-[4-[(8-methoxy-3,4-dihydro-2H-chromen-3-yl)(propyl)amino]butyl]-8-azaspiro[4.5]decane-7,9-dione		C₂₆H₃₈N₂O₄	详情	详情

Extended Information