|
【结 构 式】 
|
【药物名称】GYKI-11679, RGH-5526 【化学名称】1-(6-Morpholino-3-pyridazinyl)-2-[1-(tert-butoxycarbonyl)-2-propylidene]hydrazine 【CA登记号】69579-13-1 【 分 子 式 】C16H25N5O3 【 分 子 量 】335.40935 |
【开发单位】Gedeon Richter (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of |
合成路线1
Heating of 3,6-dichloropyridazine (I) with hydrazine hydrate at 100 C gives 6-chloro-3-pyridazinylhydrazine (II). The hydrazino group is protected by transforming it with camphor (III) to the camphorhydrazone (IV), which is aminated by heating with morpholine to give the morpholinylhydrazone (V). After liberating the hydrazine function by acidic hydrolysis in a biphasic system, the resulting 6-morpholino-3-pyridazinylhydrazine (VI) is reacted either with tert-butylacetoacetate (VII) or with tert-butylpropiolate (VIII) to yield RGH-5526.
| 【1】 Inoue, H.; Yoshida, M.; Aizawa, H.; et al.; Eur J Med Chem 1984, 19, 6, 111-117. |
| 【2】 Szilagyi, G.; et al. (Gedeon Richter Ltd.); Morpholino pyridazinylhydrazones. DE 2825861; FR 2394535; GB 2000125; HU 176972; JP 54016486; US 4259328; US 4308386 . |
| 【3】 Nogradi, M.; RGH-5526. Drugs Fut 1985, 10, 1, 32. |
| 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) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (I) | 11292 | 3,6-Dichloropyridazine | 141-30-0 | C4H2Cl2N2 | 详情 | 详情 |
| (II) | 28922 | 3-chloro-6-hydrazinopyridazine | 17284-97-8 | C4H5ClN4 | 详情 | 详情 |
| (III) | 28926 | 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one | 464-48-2 | C10H16O | 详情 | 详情 |
| (IV) | 28923 | 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one N-(6-chloro-3-pyridazinyl)hydrazone | C14H19ClN4 | 详情 | 详情 | |
| (V) | 28924 | 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one N-[6-(4-morpholinyl)-3-pyridazinyl]hydrazone | C18H27N5O | 详情 | 详情 | |
| (VI) | 24847 | 4-(6-hydrazino-3-pyridazinyl)morpholine | C8H13N5O | 详情 | 详情 | |
| (VII) | 27907 | Acetoacetic acid tert-butyl ester;3-Oxo-butanoic acid 1,1-dimethylethyl estertert-butyl 3-oxobutanoate | 1694-31-1 | C8H14O3 | 详情 | 详情 |
| (VIII) | 28925 | tert-butyl propiolate | 13831-03-3 | C7H10O2 | 详情 | 详情 |