【结 构 式】 |
【药物名称】Propiram fumarate, Bay-4503, Dirame, Algeril 【化学名称】N-[1-Methyl-2-(1-piperidinyl)ethyl]-N-(2-pyridyl)propanamide (E)-2-butenedioate (1:1) 【CA登记号】13717-04-9, 15686-91-6 (free base) 【 分 子 式 】C20H29N3O5 【 分 子 量 】391.47123 |
【开发单位】Bayer (Originator), Shire Pharmaceuticals (Licensee) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, mu-Opioid Agonists, mu-Opioid Antagonists |
合成路线1
The reduction of 1-(1-piperdinyl)acetone oxime (I) with LiAlH4 in ethyl ether, THF or dioxan gives 1-methyl2-(1-piperidinyl)ethylaine (II), which is acylated with propionyl chloride (III) in ether to afford propionamide (IV). The condensation of (IV) with 2-bromopyridine (V) by heating with K2CO3 and Cu (dust) provides compound (VI). Alternatively, (VI) can be obtained by heating N-[1-methyl-2-(1-piperidinyl)ethyl]-N-(2-pyridyl)amine (VII) with propionic anhydride (VIII). Finally, heating derivative (VI) with fumaric acid in acetone/EtOH allows formation of the desired compound as the corresponding fumarate salt.
【1】 (Almirall Prodesfarma, SA); Process for the preparation of 2-aminopyridine derivs.. ES 434325 . |
【2】 Hoffmeister, F.; Wirth, W.; Kroneberg, H.-G.; Hiltmann, R.; Wollweber, H. (Bayer AG); Pyridine derivs. and their preparation (-N-tertiaryl aminoalkyl-N-acyl)amino pyridines. DE 1232147; US 3163654 . |
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) | 47242 | 1-(1-piperidinyl)acetone oxime | C8H16N2O | 详情 | 详情 | |
(II) | 47243 | 1-methyl-2-(1-piperidinyl)ethylamine; 1-(1-piperidinyl)-2-propanamine | C8H18N2 | 详情 | 详情 | |
(III) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
(IV) | 47244 | N-[1-methyl-2-(1-piperidinyl)ethyl]propanamide | C11H22N2O | 详情 | 详情 | |
(V) | 29052 | 2-Bromopyridine;α-bromopyridine;α-bromoazine | 109-04-6 | C5H4BrN | 详情 | 详情 |
(VI) | 47245 | N-[1-methyl-2-(1-piperidinyl)ethyl]-N-(2-pyridinyl)propanamide | C16H25N3O | 详情 | 详情 | |
(VII) | 47246 | N-[1-methyl-2-(1-piperidinyl)ethyl]-2-pyridinamine; N-[1-methyl-2-(1-piperidinyl)ethyl]-N-(2-pyridinyl)amine | C13H21N3 | 详情 | 详情 | |
(VIII) | 20095 | propionic anhydride | 123-62-6 | C6H10O3 | 详情 | 详情 |