2-vinyl-1H-isoindole-1,3(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】32749

【品名】2-vinyl-1H-isoindole-1,3(2H)-dione

【CA登记号】3485-84-5

【分子式】C₁₀H₇NO₂

【分子量】173.17112

【元素组成】C 69.36% H 4.07% N 8.09% O 18.48%

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：(VII)

The reaction of 3-bromo-5-iodobenzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which by a Friedel-Crafts condensation with fluorobenzene (II) by means of AlCl3 in refluxing dichloromethane yields the benzophenone (IV). The condensation of (IV) with ethyl acrylate (V) by means of palladium acetate and triethylamine in refluxing acetonitrile affords the cinnamic acid derivative (VI), which is condensed with N-vinylphthalimide (VII) by means of palladium acetate and diisopropylamine in refluxing xylene to provide the unsaturated adduct (VIII). The reduction of the carbonyl group of (VIII) with triethylsilane and TFA gives the diphenylmethane derivative (IX), which is hydrogenated with H2 over Pd/C in ethyl acetate to yield the saturated diphenylmethane derivative (X). Elimination of the phthalimido group of (X) with hydrazine affords (XI) with a primary amino group. that is sulfonated with 4-chlorophenylsulfonyl chloride (XII) and triethylamine in THF to provide the sulfonamide (XIII). Finally, the ester group of (XIII) is hydrolyzed with aqueous NaOH.

参考文献中间体

合成目标

【1】 Waite, D.C.; Mason, C.P.; A scalable synthesis of the thromboxane receptor antagonist 3-(3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl]propionic acid via a regioselective heck cross-coupling strategy. Org Process Res Dev 1998, 2, 2, 116.

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)	32745	3-bromo-5-iodobenzoic acid	188815-32-9	C₇H₄BrIO₂	详情	详情
(II)	32746	3-bromo-5-iodobenzoyl chloride		C₇H₃BrClIO	详情	详情
(III)	17466	Fluorobenzene	462-06-6	C₆H₅F	详情	详情
(IV)	32747	(3-bromo-5-iodophenyl)(4-fluorophenyl)methanone		C₁₃H₇BrFIO	详情	详情
(V)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(VI)	32748	ethyl (E)-3-[3-bromo-5-(4-fluorobenzoyl)phenyl]-2-propenoate		C₁₈H₁₄BrFO₃	详情	详情
(VII)	32749	2-vinyl-1H-isoindole-1,3(2H)-dione	3485-84-5	C₁₀H₇NO₂	详情	详情
(VIII)	32750	ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzoyl)phenyl]-2-propenoate		C₂₈H₂₀FNO₅	详情	详情
(IX)	32751	ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzyl)phenyl]-2-propenoate		C₂₈H₂₂FNO₄	详情	详情
(X)	32752	ethyl 3-[3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-fluorobenzyl)phenyl]propanoate		C₂₈H₂₆FNO₄	详情	详情
(XI)	27001	ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₀H₂₄FNO₂	详情	详情
(XII)	15787	4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride	98-60-2	C₆H₄Cl₂O₂S	详情	详情
(XIII)	27002	ethyl 3-[3-(2-[[(4-chlorophenyl)sulfonyl]amino]ethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₆H₂₇ClFNO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

4-Bromothiophenol (I) was alkylated with tert-butyl bromoisobutyrate (II) to give the bromoester (III). Heck reaction of (III) with vinylphthalimide (IV) produced adduct (V), which was hydrogenated in the presence of Wilkinson's catalyst to yield the arylethyl phthalimide (VI). Following phthalimide deprotection with hydrazine, the resulting primary amine (VII) was coupled with heptanoic acid using diisopropyl carbodiimide and hydroxybenzotriazole affording amide (VIII). Borane reduction of (VIII) furnished the secondary amine (IX), which was condensed with 2,4-difluorophenyl isocyanate (X) to give urea (XI). Finally, trifluoroacetic acid-promoted cleavage of the tert-butyl ester of (IX) provided the title carboxylic acid.

参考文献中间体

合成目标

【1】 Brown, P.J.; Winegar, D.A.; Plunket, K.D.; et al.; A ureido thiosobutyric acid (GW9578) is a subtype selective PPARalpha agonist with potent lipid lowering activity. J Med Chem 1999, 42, 19, 3785.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	35032	heptanoic acid	111-14-8	C₇H₁₄O₂	详情	详情
(I)	29626	4-bromophenylhydrosulfide; 4-bromobenzenethiol	106-53-6	C₆H₅BrS	详情	详情
(II)	34947	tert-butyl 2-bromo-2-methylpropanoate	23877-12-5	C₈H₁₅BrO₂	详情	详情
(III)	34948	tert-butyl 2-[(4-bromophenyl)sulfanyl]-2-methylpropanoate		C₁₄H₁₉BrO₂S	详情	详情
(IV)	32749	2-vinyl-1H-isoindole-1,3(2H)-dione	3485-84-5	C₁₀H₇NO₂	详情	详情
(V)	34949	tert-butyl 2-([4-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₄H₂₅NO₄S	详情	详情
(VI)	34950	tert-butyl 2-([4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₄H₂₇NO₄S	详情	详情
(VII)	34951	tert-butyl 2-[[4-(2-aminoethyl)phenyl]sulfanyl]-2-methylpropanoate		C₁₆H₂₅NO₂S	详情	详情
(VIII)	34952	tert-butyl 2-([4-[2-(heptanoylamino)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₃H₃₇NO₃S	详情	详情
(IX)	34953	tert-butyl 2-([4-[2-(heptylamino)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₃H₃₉NO₂S	详情	详情
(X)	23255	2,4-difluorophenyl isocyanate; 2,4-difluoro-1-isocyanatobenzene	59025-55-7	C₇H₃F₂NO	详情	详情
(XI)	34954	tert-butyl 2-[(4-[2-[[(2,4-difluoroanilino)carbonyl](heptyl)amino]ethyl]phenyl)sulfanyl]-2-methylpropanoate		C₃₀H₄₂F₂N₂O₃S	详情	详情

Extended Information