methyl 4-iodobenzoate -Drug Synthesis Database

【结构式】

【分子编号】16123

【品名】methyl 4-iodobenzoate

【CA登记号】619-44-3

【分子式】C₈H₇IO₂

【分子量】262.04685

【元素组成】C 36.67% H 2.69% I 48.43% O 12.21%

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)

A new synthesis of LY-303366 has been reported: The enzymatic hydrolysis of echinocandin B (I) with Actinoplanes utahensis provides the corresponding cyclic peptide (II), which is then reacylated with the active ester 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (III) in DMF. The active ester (III) is obtained as follows: 4-Bromo-4'-(pentyloxy)biphenyl (IV) is treated with sec-butyllithium and triisopropyl borate in THF/cyclohexane, yielding (after hydrolysis with HCl) 4'-(pentyloxy)biphenyl-4-boronic acid (V), which is condensed with methyl 4-iodobenzoate (VI) by means of palladium tetrakis(triphenylphosphine) and K2CO3 in refluxing toluene, giving 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid methyl ester (VII). The hydrolysis of (VII) with NaOH in refluxing dioxane containing 2N NaOH affords the corresponding free acid (VIII), which is finally converted to the active ester (III) by esterification with 2,4,5-trichlorophenol (IX) by means of dicyclohexylcarbodiimide (DCC) in DMF.

参考文献中间体

合成目标

【1】 LaGrandeur, L.; Turner, W.W.; Debono, M.; et al.; Semisynthetic chemical modification of the antifungal lipopeptidechinocandin B (ECB): Structure-activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB. J Med Chem 1995, 38, 17, 3271.

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)	16120	(9Z,12Z)-N-[(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-9,12-octadecadienamide		C₅₂H₈₁N₇O₁₆	详情	详情
(II)	16118	(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-9-amino-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methylhexadecahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosine-5,8,14,19,22,25(9H,25aH)-hexone		C₃₄H₅₁N₇O₁₅	详情	详情
(III)	16119	4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester		C₃₀H₂₅Cl₃O₃	详情	详情
(IV)	16121	4-bromo-4'-(pentyloxy)-1,1'-biphenyl; 4'-bromo[1,1'-biphenyl]-4-yl pentyl ether		C₁₇H₁₉BrO	详情	详情
(V)	16122	4'-(Pentyloxy)biphenyl-4-ylboronic acid		C₁₇H₂₁BO₄	详情	详情
(VI)	16123	methyl 4-iodobenzoate	619-44-3	C₈H₇IO₂	详情	详情
(VII)	16124	4''-Pentyloxy-p-terphenyl-4-carboxylic acid methyl ester		C₂₅H₂₆O₃	详情	详情
(VIII)	16125	4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid		C₂₄H₂₄O₃	详情	详情
(IX)	16126	2,4,5-trichlorophenol	95-95-4	C₆H₃Cl₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Organozinc reagent (II), prepared from 4-bromo-1,2-dimethoxybenzene (I), was coupled with methyl iodobenzoate (III) in the presence of bis(triphenylphosphine) palladium dichloride and diisobutylaluminum hydride to furnish biphenyl derivative (IV). After saponification of the methyl ester group of (IV), treatment with thionyl chloride yielded acid chloride (V).

参考文献中间体

合成目标

【1】 Gong, Y.; Guertin, K.R.; McGarry, D.G.; Pauls, H.W.; Klein, S.I.; Spada, A.P. (Aventis Pharmaceuticals, Inc.); Substd. N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides. CA 2264556; EP 0931060; WO 9900356 .

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)	38452	4-bromo-1,2-dimethoxybenzene; 4-bromo-2-methoxyphenyl methyl ether	2859-78-1	C₈H₉BrO₂	详情	详情
(II)	38453	chloro(3,4-dimethoxyphenyl)zinc		C₈H₉ClO₂Zn	详情	详情
(III)	16123	methyl 4-iodobenzoate	619-44-3	C₈H₇IO₂	详情	详情
(IV)	38454	methyl 3',4'-dimethoxy[1,1'-biphenyl]-4-carboxylate		C₁₆H₁₆O₄	详情	详情
(V)	38455	3',4'-dimethoxy[1,1'-biphenyl]-4-carbonyl chloride		C₁₅H₁₃ClO₃	详情	详情

Extended Information