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【结 构 式】 
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【分子编号】15468 【品名】1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether 【CA登记号】 |
【 分 子 式 】C20H25NO4 【 分 子 量 】343.42284 【元素组成】C 69.95% H 7.34% N 4.08% O 18.64% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of acryloyl chloride (I) with pentane-1,5-diol (II) by means of triethylamine and pyrogalol in hot benzene gives 1,5-pentamethylene diacrylate (III), which is condensed with tetrahydropapaverine (IV) in refluxing benzene to afford N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-bis(tetrahydropapaverine) (V). Finally, this compound is quaternized by treatment with methyl benzenesulfonate in acetonitrile.
| 【1】 Dewar, G.H.; Dhar, N.C.; Sternlake, J.B.; Urwin, R.J.; Waigh, R.D. (Glaxo Wellcome Inc.); Quarternary ammonium compounds. DE 2655883; FR 2334359; JP 52077069; US 4179507 . |
| 【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; Atracurium Besilate. Drugs Fut 1980, 5, 11, 541. |
| 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) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (II) | 15471 | 1,5-pentanediol | 111-29-5 | C5H12O2 | 详情 | 详情 |
| (III) | 15470 | 5-(acryloyloxy)pentyl acrylate; 1,6-Hexanediol Diacrylate | 36840-85-4 | C11H16O4 | 详情 | 详情 |
| (IV) | 15468 | 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether | C20H25NO4 | 详情 | 详情 | |
| (V) | 15473 | 5-([3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoyl]oxy)pentyl 3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoate | C51H66N2O12 | 详情 | 详情 | |
| (VI) | 15474 | methyl benzenesulfonate | 80-18-2 | C7H8O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The optical resolution of (±)-tetrahydropapaverine (I) with N-acetyl-L-leucine yields (R)-tetrahydropapaverine (II), which is condensed with 1,5-pentamethylene diacrylate (III) (obtained by esterification of 1,5-pentanediol (IV) with 3-bromopropionic acid by means of p-toluenesulfonic acid followed by dehydromination with triethylamine) in hot glacial acetic acid and treated with oxalic acid to afford the bis-tetrahydropapaverine derivative (VI). Finally, this compound is treated with aqueous Na2CO3 to eliminate the oxalic acid and then treated with methyl benezenesulfonate (VII) at room temperature. The resulting product is a 58:34:6 mixture of the (1R-cis, 1'R-cis)- (1R-cis, 1'R-trans)- and (1R-trans, 1'R-trans)-isomers, which is resolved by column chromatography over silica gel using an 80:20:5 mixture of dichloromethane methanol and methanesulfonic acid.
| 【1】 Mealy, N.; Castaner, J.; Cisatracurium Besylate. Drugs Fut 1996, 21, 1, 14. |
| 【2】 Hill, D.A.; Turner, G.L. (Glaxo Wellcome plc); Neuromuscular blocking agents. CH 683427; EP 0539470; FR 2665791; GB 2260763; JP 1993508648; JP 1998139763; US 5453510; WO 9200965 . |
| 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) | 15468 | 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether | C20H25NO4 | 详情 | 详情 | |
| (II) | 15469 | (1R)-1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether; (1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | C20H25NO4 | 详情 | 详情 | |
| (III) | 15470 | 5-(acryloyloxy)pentyl acrylate; 1,6-Hexanediol Diacrylate | 36840-85-4 | C11H16O4 | 详情 | 详情 |
| (IV) | 15471 | 1,5-pentanediol | 111-29-5 | C5H12O2 | 详情 | 详情 |
| (V) | 15472 | 3-Bromopropionic acid | 590-92-1 | C3H5BrO2 | 详情 | 详情 |
| (VI) | 15473 | 5-([3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoyl]oxy)pentyl 3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoate | C51H66N2O12 | 详情 | 详情 | |
| (VII) | 15474 | methyl benzenesulfonate | 80-18-2 | C7H8O3S | 详情 | 详情 |