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【结 构 式】 
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【分子编号】50202 【品名】3,4-di(1,3-dioxolan-2-yl)benzoic acid 【CA登记号】 |
【 分 子 式 】C13H14O6 【 分 子 量 】266.25056 【元素组成】C 58.65% H 5.3% O 36.05% |
合成路线1
该中间体在本合成路线中的序号：(IX)Treatment of naltrexone hydrochloride (I) with 2-nitrophenylhydrazine (II) under Fischer conditions in HCl:HOAc provides nitroindole derivative (III), which is reduced by means of hydrazine and Ni Raney in EtOH to afford amine (IV). Separately, 3,4-dimethylbenzoic acid (V) is brominated with NBS and benzoyl peroxide in refluxing CCl4 to furnish tetrabromo derivative (VI), which is then hydrolyzed with Na2CO3 in H2O to yield 3,4-diformylbenzoic acid (VII). Bis acetalization of (VII) with ethylene glycol (VIII) in benzene in the presence of p-TsOH affords carboxylic acid (IX), which is then coupled with intermediate (IV) by means of DCC and HOBt in DMF to give the corresponding amido ester derivative (X). Selective saponification of (X) with K2CO3 in MeOH affords amide (XI), which is finally converted into the target compound by hydrolysis with HCl in acetone.
| 【1】 Portoghese, P.S.; et al.; delta Opioid antagonist activity and binding studies of regioisomeric isothiocyanate derivatives of naltrindole: Evidence for delta receptor subtypes. J Med Chem 1992, 35, 22, 4086. |
| 【3】 Le Bourdonnec, B.; et al.; Reporter affinity labels: An o-phthalaldehyde derivative of beta-naltrexamide as a fluorogenic ligand for opioid receptors. J Med Chem 2000, 43, 13, 2489. |
| 【2】 Poda, G.; Loh, H.H.; Le Bourdonnec, B.; Law, P.Y.; WEl Kouhen, R.; Portoghese, P.S.; Ferguson, D.M.; Covalently induced activation of the delta opioid receptor by a fluorogenic affinity label, 7'-(phthalaldehyde-carboxamido)naltrindole (PNTI). J Med Chem 2001, 44, 7, 1017. |
| 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) | 37822 | (1S,5R,13R,17R)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C20H23NO4 | 详情 | 详情 | |
| (II) | 50196 | 1-(2-nitrophenyl)hydrazine | C6H7N3O2 | 详情 | 详情 | |
| (III) | 50197 | (1S,2R,13R,21R)-22-(cyclopropylmethyl)-9-nitro-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H25N3O5 | 详情 | 详情 | |
| (IV) | 50198 | (1S,2R,13R,21R)-9-amino-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H27N3O3 | 详情 | 详情 | |
| (V) | 50199 | 3,4-Dimethylbenzoic acid; o-Xylene-4-carboxylic acid | 619-04-5 | C9H10O2 | 详情 | 详情 |
| (VI) | 50200 | 3,4-bis(dibromomethyl)benzoic acid | C9H6Br4O2 | 详情 | 详情 | |
| (VII) | 50201 | 3,4-bis(2-oxoethyl)benzoic acid | C11H10O4 | 详情 | 详情 | |
| (VIII) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (IX) | 50202 | 3,4-di(1,3-dioxolan-2-yl)benzoic acid | C13H14O6 | 详情 | 详情 | |
| (X) | 50203 | (1S,2R,13R,21R)-22-(cyclopropylmethyl)-9-[[3,4-di(1,3-dioxolan-2-yl)benzoyl]amino]-2-hydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-16-yl 3,4-di(1,3-dioxolan-2-yl)benzoate | C52H51N3O13 | 详情 | 详情 | |
| (XI) | 50204 | N-[(1S,2R,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-9-yl]-3,4-di(1,3-dioxolan-2-yl)benzamide | C39H39N3O8 | 详情 | 详情 |