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【结 构 式】 
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【分子编号】35608 【品名】2-(4-[[(6-amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-5-pyrimidinyl)imino]methyl]phenoxy)acetic acid 【CA登记号】 |
【 分 子 式 】C19H24N4O5 【 分 子 量 】388.42352 【元素组成】C 58.75% H 6.23% N 14.42% O 20.6% |
合成路线1
该中间体在本合成路线中的序号：(IV)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.
| 【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2
该中间体在本合成路线中的序号：(IV)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.
| 【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 |