3-bromo-5,6,7-trimethoxy-2-benzofuran-1(3H)-one -Drug Synthesis Database

【结构式】

【分子编号】34422

【品名】3-bromo-5,6,7-trimethoxy-2-benzofuran-1(3H)-one

【CA登记号】

【分子式】C₁₁H₁₁BrO₅

【分子量】303.10934

【元素组成】C 43.59% H 3.66% Br 26.36% O 26.39%

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：(XXIV)

The oxidative ring opening of 2-oxa-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXIII) with NaOH in methanol, followed by a treatment with CrO2Cl2 in CCl4 gives 2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)-1-cyclopentanone (XXIV), which by reaction with methyl trimethylsilylacetate (XXV) by means of butyllithium and diisopropylamine in THF is converted into 1-(methoxycarbonylmethylidene)-2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVI). The hydrogenation of (XXVI) with H2 over Pd/C in ethanol affords 1,2-bis(methoxycarbonylmethyl)-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVII), which is cyclized by means of potassium tert-butoxide in refluxing benzene to 2 (or 4)-methoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXVIII). Finally, this compound is hydrolyzed and decarboxylated in HMPT - water at 160 C giving the ketone (VIII), already obtained.

参考文献中间体

合成目标

【1】 Hayashi, M.; Konishi, Y.; Arai, Y.; 6,9-Methano-PGI2 analogues. CH 639360; DE 2912409; FR 2422635; GB 2017699; IT 1113341; US 4479966 .
【2】 Kottegoda, S.R.; Serradell, M.N.; Adaikan, P.G.; Castaner, J.; ONO-41483. Drugs Fut 1984, 9, 11, 833.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVIIIa)	34426	tert-butyl (2S)-2,5-diamino-5-oxopentanoate		C₉H₁₈N₂O₃	详情	详情
(XVIIIb)	34427	tert-butyl (2S)-5-amino-2-(4-nitro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-oxopentanoate		C₁₇H₁₉N₃O₇	详情	详情
(XXIII)	34421	5,6,7-trimethoxy-2-benzofuran-1(3H)-one		C₁₁H₁₂O₅	详情	详情
(XXIV)	34422	3-bromo-5,6,7-trimethoxy-2-benzofuran-1(3H)-one		C₁₁H₁₁BrO₅	详情	详情
(XXV)	34423	1-naphthylmethylphosphonic acid	4730-77-2	C₁₁H₁₁O₃P	详情	详情
(XXVI)	34424	4-nitro-1H-isoindole-1,3(2H)-dione；3-nitrophthalimide	603-62-3	C₈H₄N₂O₄	详情	详情
(XXVII)	34425	ethyl 4-nitro-1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate		C₁₁H₈N₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Iodination of 3,4,5-trimethoxybenzyl alcohol (I) with iodine in the presence of silver trifluoroacetate gave the 2-iodobenzyl alcohol (II). Subsequent palladium-catalyzed carbonylation-lactonization reaction with (II) gave rise to phthalide (III). This was brominated using NBS to afford the 3-bromophthalide (IV). Finally, condensation of (IV) with (1-naphthyl)methylphosphonic acid (V) yielded the title bisphthalidyl phosphonate.

参考文献中间体

合成目标

【1】 Dang, Q.; et al.; Synthesis of phosphonate 3-phthalidyl esters as prodrugs for potential intracellular delivery of phosphonates. Bioorg Med Chem Lett 1999, 9, 11, 1505.

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)	23613	(3,4,5-trimethoxyphenyl)methanol	3840-31-1	C₁₀H₁₄O₄	详情	详情
(II)	34420	(2-iodo-3,4,5-trimethoxyphenyl)methanol		C₁₀H₁₃IO₄	详情	详情
(III)	34421	5,6,7-trimethoxy-2-benzofuran-1(3H)-one		C₁₁H₁₂O₅	详情	详情
(IV)	34422	3-bromo-5,6,7-trimethoxy-2-benzofuran-1(3H)-one		C₁₁H₁₁BrO₅	详情	详情
(V)	34423	1-naphthylmethylphosphonic acid	4730-77-2	C₁₁H₁₁O₃P	详情	详情

Extended Information