2-iodoacetic acid -Drug Synthesis Database

【结构式】

【分子编号】40086

【品名】2-iodoacetic acid

【CA登记号】64-69-7

【分子式】C₂H₃IO₂

【分子量】185.94909

【元素组成】C 12.92% H 1.63% I 68.25% O 17.21%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(C)

The condensation of 2,3-dichloroanisole (I) with phenylacetyl chloride (A) by means of AlCl3 in CS2 gives 2,3-dichloro-4-phenylacetylanisole (II), which by reaction with bis(dimethylamino)methane (B) in acetic anhydride is converted into 2,3-dichloro-4-(2-phenylacryloyl)anisole (III). The cyclization of (III) by means of H2SO4 yields 6,7-dichloro-2-phenyl-5-methoxy-1-indanone (IV), which by demethylation with pyridine hydrochloride at 190 C yields 6,7-dichloro-2-phenyl-5-hydroxy-1-indadone (V). The treatment of the phenol (V) with iodoacetic acid (C) and K2CO3 in acetone affords 6,7-dichloro-2-phenyl-1-oxo-5-indanyloxyacetic acid (VI), which is finally methylated with methyl iodide and NaH in DMF.

参考文献中间体

合成目标

【1】 Cragoe, E.J. Jr.; Woltersdorf, O.W. Jr. (Merck & Co., Inc.); Substituted indanones. DE 2448454; ES 430900; FR 2247218; GB 1474459 .
【2】 Castaner, J.; Chatterjee, S.S.; MK 196. Drugs Fut 1977, 2, 3, 179.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	14349	N,N,N,N-tetramethylmethanediamine; tetramethylmethylenediamine;bis(dimethylamino)methane; N-[(dimethylamino)methyl]-N,N-dimethylamine	51-80-9	C₅H₁₄N₂	详情	详情
(A)	25890	2-phenylacetyl chloride；Phenylacetyl chloride;Phenacetyl chloride;Benzeneacetyl chloride	103-80-0	C₈H₇ClO	详情	详情
(I)	40081	1,2-dichloro-3-methoxybenzene; 2,3-dichlorophenyl methyl ether	1984-59-4	C₇H₆Cl₂O	详情	详情
(II)	40082	1-(2,3-dichloro-4-methoxyphenyl)-2-phenyl-1-ethanone		C₁₅H₁₂Cl₂O₂	详情	详情
(III)	40083	1-(2,3-dichloro-4-methoxyphenyl)-2-phenyl-2-propen-1-one		C₁₆H₁₂Cl₂O₂	详情	详情
(IV)	40084	6,7-dichloro-5-methoxy-2-phenyl-1-indanone		C₁₆H₁₂Cl₂O₂	详情	详情
(V)	40085	6,7-dichloro-5-hydroxy-2-phenyl-1-indanone		C₁₅H₁₀Cl₂O₂	详情	详情
(VI)	40087	2-[(6,7-dichloro-1-oxo-2-phenyl-2,3-dihydro-1H-inden-5-yl)oxy]acetic acid		C₁₇H₁₂Cl₂O₄	详情	详情
(C)	40086	2-iodoacetic acid	64-69-7	C₂H₃IO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Alkylation of 4-hydroxybenzaldehyde (I) with iodoacetic acid in the presence of K2CO3 afforded ether (II). Subsequent condensation of (II) with 5,6-diamino-1,3-dipropyluracil (III) gave imine (IV). Oxidative ring closure by means of FeCl3 in boiling EtOH, with concomitant esterification, furnished xanthine (V). The ethyl ester of (V) was then displaced by hydrazine to yield hydrazide (VI). Finally, condensation of (VI) with dimethylmaleic anhydride (VII) gave rise to the corresponding maleimide.

参考文献中间体

合成目标

【1】 Jacobson, K.A.; et al.; Functionalized congeners of 1,3-dialkylxanthines: preparation of analogues with high affinity for adenosine receptors. J Med Chem 1985, 28, 9, 1334-40.
【2】 Karton, Y.; Melman, N.; Ji, X.-D.; Jacobson, K.A.; Linden, J.; Kim, Y.-C.; Acyl-hydrazide derivatives of a xanthine carboxylic congener (XCC) as selective antagonists at human A2B adenosine receptors. Drug Dev Res 1999, 47, 4, 178.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40086	2-iodoacetic acid	64-69-7	C₂H₃IO₂	详情	详情
(I)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	25513	2-(4-Formylphenoxy)acetic acid; 4-Formyl phenoxy acetic acid	22042-71-3	C₉H₈O₄	详情	详情
(III)	14628	5,6-diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione		C₁₀H₁₈N₄O₂	详情	详情
(IV)	35608	2-(4-[[(6-amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-5-pyrimidinyl)imino]methyl]phenoxy)acetic acid		C₁₉H₂₄N₄O₅	详情	详情
(V)	35609	ethyl 2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy]acetate		C₂₁H₂₆N₄O₅	详情	详情
(VI)	35610	2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy]acetohydrazide		C₁₉H₂₄N₆O₄	详情	详情
(VII)	35611	3,4-dimethyl-2,5-furandione	766-39-2	C₆H₆O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：

Alkylation of 4-hydroxybenzaldehyde (I) with iodoacetic acid afforded 4-formylphenoxyacetic acid (II). This was condensed with 5,6-diamino-1,3-dipropyluracil (III) to produce imine (IV), which was oxidatively cyclized to xanthine (V) in the presence of ferric chloride. After activation of (V) as the corresponding acid chloride (VI), coupling with 4-aminobenzonitrile (VII) furnished the title amide.

参考文献中间体

合成目标

【1】 Jacobson, K.A.; et al.; Functionalized congeners of 1,3-dialkylxanthines: preparation of analogues with high affinity for adenosine receptors. J Med Chem 1985, 28, 9, 1334-40.
【2】 Ji, X.; Kim, Y.-C.; Linden, J.; Jacobson, K.A.; Melman, N.; Anilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A2B adenosine receptors. J Med Chem 2000, 43, 6, 1165.
【3】 Kim, Y.-C.; Linden, J.M.; Jocobson, K.A. (University of Virginia); Substd. 8-phenylxanthines useful as antagonists of A2B adenosine receptors. WO 0073307 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40086	2-iodoacetic acid	64-69-7	C₂H₃IO₂	详情	详情
(I)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	25513	2-(4-Formylphenoxy)acetic acid; 4-Formyl phenoxy acetic acid	22042-71-3	C₉H₈O₄	详情	详情
(III)	14628	5,6-diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione		C₁₀H₁₈N₄O₂	详情	详情
(IV)	35608	2-(4-[[(6-amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-5-pyrimidinyl)imino]methyl]phenoxy)acetic acid		C₁₉H₂₄N₄O₅	详情	详情
(V)	44758	2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy]acetic acid		C₁₉H₂₂N₄O₅	详情	详情
(VI)	44759	2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy]acetyl chloride		C₁₉H₂₁ClN₄O₄	详情	详情
(VII)	15361	4-Aminobenzonitrile	873-74-5	C₇H₆N₂	详情	详情

Extended Information