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【结 构 式】 
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【分子编号】28771 【品名】2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5-carbaldehyde 【CA登记号】 |
【 分 子 式 】C11H13NO3 【 分 子 量 】207.22916 【元素组成】C 63.76% H 6.32% N 6.76% O 23.16% |
合成路线1
该中间体在本合成路线中的序号：(I)The Grignard reaction of 2,2,8-trimethyl-5-formylpyrido[4,3-e]-1,3-dioxane (I) with 4-chlorophenyl magnesium bromide (II) in refluxing ether gives 2,2,8-trimethyl-5-(4-chloro-alpha-hydroxybenzyl)pyrido[4,3-e]-1,3-dioxane (III), which is then hydrolyzed and cyclized by a treatment with aqueous concentrated HCl
| 【1】 Esanu, A (SCRAS (Societe de Conseils de Recherches et d'Applications Scientifiques)); Furo[3,4-c]pyridine derivatives and their pharmaceutical use. BE 0891797; DE 3204596; FR 2499406; FR 2499574; GB 2092586; JP 82150688; US 4383998 . |
| 【2】 Castaner, J.; Serradell, M.N.; Thorpe, P.; Cycletanide. Drugs Fut 1985, 10, 5, 378. |
合成路线2
该中间体在本合成路线中的序号：(I)The synthesis of (rac)-BN-1267 is presented. The Grignard reaction of 2,2,8-trimethyl-5-formylpyrido[4,3-e]-1,3-dioxane (I) with 4-chloro phenyl magnesium bromide in refluxing ether gives 2,2,8-trimethyl-5-(4-chloro-alpha-hydroxybenzyl)pyrido[4,3-e]-1,3-dioxane (II), which by oxidation with MnO2 affords the corresponding ketone (III). The Grignard reaction of (III) with methyl maynesium iodide gives 2,2,8-trimethyl-5-(4-chloro-alpha-methyl-alpha-hydraxybenzyl)pyrido[4,3-e]-1,3-dioxane (IV), which is then hydrolyzed and cyclized by treatment with aqueous concentrated HCl.
| 【1】 De Salvia, R.; et al.; J Meet Franco-Ital Pharmacol Soc (June, Paris) 1984, 135, 1-2, 1. |
| 【2】 Esanu, A. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Furo[3,4-c]pyridine derivatives and therapeutic compositions containing the same. BE 0899222; CH 660191; GB 2137618; JP 1984193888; US 4581363; US 4735950 . |
| 【3】 Esanu, A.; Etienne, A.; Laurent, J.-P.; Braquet, P.; Mencia Huerta, J.M. Clostre, F.; Touvay, C.; Clofurenadine hydrochloride. Drugs Fut 1987, 12, 7, 627. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 25127 | bromo(4-chlorophenyl)magnesium | 873-77-8 | C6H4BrClMg | 详情 | 详情 |
| (I) | 28771 | 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5-carbaldehyde | C11H13NO3 | 详情 | 详情 | |
| (II) | 28772 | (3-chlorophenyl)(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methanol | C17H18ClNO3 | 详情 | 详情 | |
| (III) | 28773 | (3-chlorophenyl)(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methanone | C17H16ClNO3 | 详情 | 详情 | |
| (IV) | 28774 | 1-(3-chlorophenyl)-1-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)-1-ethanol | C18H20ClNO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Addition of di-tert-butyl phosphite (II) to the pyridine aldehyde (I) afforded the pyridylphosphonate (III). The tert-butyl phosphonate esters and the cyclic ketal groups of (III) were then hydrolyzed under acidic conditions to furnish the title compound.
| 【1】 Haque, W. (Medicure Inc.); Cardioprotective phosphonates and malonates. WO 0164692 . |
| 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) | 28771 | 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5-carbaldehyde | C11H13NO3 | 详情 | 详情 | |
| (II) | 42237 | di(tert-butyl) phosphonate | 13086-84-5 | C8H19O3P | 详情 | 详情 |
| (III) | 53403 | di(tert-butyl) hydroxy(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methylphosphonate | n/a | C19H32NO6P | 详情 | 详情 |