1,3-Benzodioxole-5-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】10125

【品名】1,3-Benzodioxole-5-carboxylic acid

【CA登记号】94-53-1

【分子式】C₈H₆O₄

【分子量】166.13324

【元素组成】C 57.84% H 3.64% O 38.52%

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：(II)

The synthesis of [14]-labeled stiripentol has been published: The reaction of 3,4-methylenedioxybromobenzene (I) with 14CO2 by means of butyllithium in ether gives 3,4-methylenedioxybenzoic acid (II), which is reduced with LiAlH4 to the corresponding benzyl alcohol (III). Oxidation of (III) with CrO3-pyridine affords the aldehyde (IV), which is condensed with methyl tert-butyl ketone (V) by means of NaOH in refluxing ethanol to give the labeled pentanone (VI). Finally, this compound is reduced to [14C]-labeled stiripentol with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Lepage, F. Veyre, A.; Madelmont, J.C.; Labarre, P.; Maurizis, J.C.; Rapp, M.; Dupuy, J.M.; Labelling by 14C and 3H of 4,4-dimethyl-1-(3,4-methylenedioxyphenyl)-1-pentene-3-ol or stiripentol. J Label Compd Radiopharm 1992, 31, 11, 961.

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)	10124	5-Bromo-1,3-benzodioxole; 4-Bromo-1,2-(methylenedioxy)benzene	2635-13-4	C₇H₅BrO₂	详情	详情
(II)	10125	1,3-Benzodioxole-5-carboxylic acid	94-53-1	C₈H₆O₄	详情	详情
(II)	44584	1,3-benzodioxole-5-carboxylic acid		C₈H₆O₄	详情	详情
(III)	10126	1,3-Benzodioxol-5-ylmethanol; Helioalcohol	495-76-1	C₈H₈O₃	详情	详情
(III)	44585	1,3-benzodioxol-5-ylmethanol		C₈H₈O₃	详情	详情
(IV)	10127	1,3-Benzodioxole-5-carbaldehyde; Heliotropine	120-57-0	C₈H₆O₃	详情	详情
(IV)	44586	1,3-benzodioxole-5-carbaldehyde		C₈H₆O₃	详情	详情
(V)	10128	3,3-Dimethyl-2-butanone; Pinacolin	75-97-8	C₆H₁₂O	详情	详情
(VI)	10129	(E)-1-(1,3-Benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-one		C₁₄H₁₆O₃	详情	详情
(VI)	44587	(E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-one		C₁₄H₁₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

N-Benzoylisonipecotic acid (I) was chlorinated with SOCl2 to produce the corresponding acid chloride (II). Acylation of the lithium enolate of (4-methoxyphenyl)acetone (III) with acid chloride (II) provided a mixture of diketone regioisomers (IV) and (V); these were separated by column chromatography. The desired diketone (IV) was then cyclized with guanidine (VI) in hot pyridine to afford the pyrimidine (VII). Basic hydrolysis of the benzamide function of (VII) gave the piperidine derivative (VIII). The target amide was finally prepared by acylation of (VIII) with 3,4-methylenedioxybenzoic acid (IX) in the presence of EDC.

参考文献中间体

合成目标

【1】 Kawakami, H.; Kurimoto, A.; Murata, S.; Fujita, H.; Iwai, K.; Fujiwara, N.; Synthesis and bioactivities of novel piperidylpyrimidine derivatives: Inhibitors of tumor necrosis factor-alpha production. Bioorg Med Chem Lett 2000, 10, 12, 1317.
【2】 Fujiwara, N.; Ueda, Y.; Murata, S.; Hirota, F.; Kawakami, H.; Fujita, H. (Sumitomo Pharmaceuticals Co., Ltd.); Piperidinylpyramidine derivs.. EP 0892795; JP 2001511764; US 5948786; WO 9738992 .

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)	52892	1-benzoyl-4-piperidinecarboxylic acid		C₁₃H₁₅NO₃	详情	详情
(II)	52893	1-benzoyl-4-piperidinecarbonyl chloride		C₁₃H₁₄ClNO₂	详情	详情
(III)	10038	4-Methoxyphenylacetone; 1-(4-Methoxyphenyl)acetone	122-84-9	C₁₀H₁₂O₂	详情	详情
(IV)	52894	1-(1-benzoyl-4-piperidinyl)-4-(4-methoxyphenyl)-1,3-butanedione		C₂₃H₂₅NO₄	详情	详情
(V)	52895	1-(1-benzoyl-4-piperidinyl)-2-(4-methoxyphenyl)-1,3-butanedione		C₂₃H₂₅NO₄	详情	详情
(VI)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(VII)	52896	{4-[2-amino-6-(4-methoxybenzyl)-4-pyrimidinyl]-1-piperidinyl}(phenyl)methanone		C₂₄H₂₆N₄O₂	详情	详情
(VIII)	52897	4-(4-methoxybenzyl)-6-(4-piperidinyl)-2-pyrimidinamine; 4-(4-methoxybenzyl)-6-(4-piperidinyl)-2-pyrimidinylamine		C₁₇H₂₂N₄O	详情	详情
(IX)	10125	1,3-Benzodioxole-5-carboxylic acid	94-53-1	C₈H₆O₄	详情	详情

Extended Information