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【结 构 式】 
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【药物名称】F-10981 【化学名称】N-[2-[1-(2H-1-Benzopyran-3-ylmethyl)piperidin-4-yl]ethyl]-N'-phenylurea 【CA登记号】202002-60-6 【 分 子 式 】C24H29N3O2 【 分 子 量 】391.51763 |
【开发单位】Pierre Fabre (Originator) 【药理作用】Antiparkinsonian Drugs, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, alpha2-Adrenoceptor Antagonists |
合成路线1
Condensation of 2-(1-benzyl-4-piperidinyl)ethyl amine (I) with phenyl isocyanate (II) provided the corresponding urea (III), which was debenzylated by hydrogenolysis over Pd/C to afford the secondary amine (IV). Subsequent Mannich reaction of (IV) with 4-chromanone (V) and paraformaldehyde produced the (chromanylmethyl)piperidine (VI). After ketone reduction of (IV) by means of NaBH4, the resulting alcohol (VII) was dehydrated in refluxing 6 N HCl to furnish the target chromene.
| 【1】 Mayer, P.; et al.; Modulation of the benzodioxane heterocycle in a novel series of potent alpha2 adrenoceptor antagonists. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 112. |
| 【2】 Vidaluc, J.-L.; Imberg, T.; Marien, M.; Briley, M. (Pierre Fabre Medicament); Novel benzodioxanes and 1-(2H)-benzopyranes, their preparation and their use as medicine. WO 9802435 . |
| 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) | 17606 | 2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine | C14H22N2 | 详情 | 详情 | |
| (II) | 11289 | 1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate | 103-71-9 | C7H5NO | 详情 | 详情 |
| (III) | 25201 | N-[2-(1-benzyl-4-piperidinyl)ethyl]-N'-phenylurea | C21H27N3O | 详情 | 详情 | |
| (IV) | 25202 | N-phenyl-N'-[2-(4-piperidinyl)ethyl]urea | C14H21N3O | 详情 | 详情 | |
| (V) | 14461 | 2,3-Dihydro-4H-chromen-4-one; 4-Chromanone | 491-37-2 | C9H8O2 | 详情 | 详情 |
| (VI) | 25203 | N-(2-[1-[(4-oxo-3,4-dihydro-2H-chromen-3-yl)methyl]-4-piperidinyl]ethyl)-N'-phenylurea | C24H29N3O3 | 详情 | 详情 | |
| (VII) | 25204 | N-(2-[1-[(4-hydroxy-3,4-dihydro-2H-chromen-3-yl)methyl]-4-piperidinyl]ethyl)-N'-phenylurea | C24H31N3O3 | 详情 | 详情 |