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【结 构 式】 
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【药物名称】GYKI-12743 【化学名称】(±)-2-[3-[N-(2-Benzo[1,4]dioxanyl)methylamino]propyl]-3(2H)-pyridazinone hydrochloride 【CA登记号】110714-10-8 【 分 子 式 】C16H20ClN3O3 【 分 子 量 】337.8091 |
【开发单位】Gedeon Richter (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, alpha-Adrenoceptor Antagonists |
合成路线1
Title compound can be prepared as shown in Scheme: 1) 3,6-Dichloropyridazine (I) is converted to 3(2H)-pyridazinone (III) in two steps. 2) 3-N-(2-Benzo[1,4]dioxanylmethyl)amino-1-propanol (V), obtained by the reaction of (2-benzo[1,4]dioxanylmethyl)-4-toluenesulfonate (IV) with 3-amino-1-propanol, is N-benzylated to form the N-protected amino alcohol (VI), which on treatment with thionyl chloride affords the chloroalkyl derivative (VII). 3) Alkylation of 3(2H)-pyridazinone (III) with (VII) under phase-transfer catalysis conditions to the N-benzylated GYKI-12743 (VIII) and then removal of the N-benzyl group by hydrogenation gives GYKI-12743.
| 【1】 Kasztreiner, E.; Rabloczky, G.; Makk, N.; Jaszlits, L.; Matyus, P.; Cseh, G.; Pribusz, geb. Rapp, I.; Czakó, K.; Diesler, E.; Elekes, I.; Kaufer, L.; Kuhár, geb. Kürthy, M.; Kincsessy, J.; Kosáry, J.; Nagy, Gyöngyi geb. C. (Richter Gedeon Vegyeszeti); 3(2H)-Pyridazinone derivs., a process and intermediates for preparing them and medicaments containing them and/or other 3(2H)-pyridazinone derivatives. AU 8664496; EP 0220735; JP 87161768 . |
| 【2】 Kasztreiner, E.; Matyus, P.; Rabloczky, G.; Jaszlits, L.; GYKI-12743. Drugs Fut 1989, 14, 7, 622. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 18522 | 3-amino-1-propanol | 156-87-6 | C3H9NO | 详情 | 详情 | |
| 19171 | 1-(Chloromethyl)benzene; Benzyl chloride | 100-44-7 | C7H7Cl | 详情 | 详情 | |
| (I) | 11292 | 3,6-Dichloropyridazine | 141-30-0 | C4H2Cl2N2 | 详情 | 详情 |
| (II) | 20957 | 6-chloro-3(2H)-pyridazinone | C4H3ClN2O | 详情 | 详情 | |
| (III) | 20958 | 3(2H)-pyridazinone | C4H4N2O | 详情 | 详情 | |
| (IV) | 20959 | 2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate | C16H16O5S | 详情 | 详情 | |
| (V) | 20960 | 3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol | C12H17NO3 | 详情 | 详情 | |
| (VI) | 20961 | 3-[benzyl(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol | C19H23NO3 | 详情 | 详情 | |
| (VII) | 20962 | N-benzyl-3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine; N-benzyl-N-(3-chloropropyl)-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amine | C19H22ClNO2 | 详情 | 详情 | |
| (VIII) | 20963 | 2-[3-[benzyl(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]propyl]-3(2H)-pyridazinone | C23H25N3O3 | 详情 | 详情 |