【结 构 式】 |
【分子编号】58543 【品名】ethyl 4-cyano-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 【CA登记号】 |
【 分 子 式 】C12H12N4O2 【 分 子 量 】244.25304 【元素组成】C 59.01% H 4.95% N 22.94% O 13.1% |
合成路线1
该中间体在本合成路线中的序号:(VI)The condensation between diethyl ethoxymethylenemalonate (I) and 5-amino-1-ethylpyrazole (II) afforded the enamino malonate (III). Cyclization of (III) upon heating at 255 C in diphenyl ether produced the pyrazolopyridine (IV). This was subsequently chlorinated to (V) in refluxing phosphoryl chloride. Alternatively, enamino malonate (III) was directly converted to the chloro pyrazolopyridine (V) by treatment with POCl3. Nitrile (VI) was prepared by displacement of the chloro group of (V) with cyanide in the presence of a phase-transfer catalyst. Cyclization of the cyano ester (VI) with hydrazine led to the pyrazolopyridopyridiazine tricyclic system (VII). Diazotization of amine (VII) generated the dioxo derivative (VIII), which was chlorinated with POCl3 to yield the dichloro derivative (IX). Selective displacement of the 6-chloro group of (IX) with the imidazole carboxamide (X) produced the imidazolyl derivative (XI).
【1】 Kim, S.; Wang, Y.; Yu, G.; Macor, J.; Chung, H.-J.; Humora, M.; Katipally, K. (Bristol-Myers Squibb Co.); Fused pyridopyridazine inhibitors of cGMP phosphodiesterase. EP 1165521; JP 2002540102; US 6316438; WO 0056719 . |
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) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
(II) | 40098 | 1-ethyl-1H-pyrazol-5-amine; 1-ethyl-1H-pyrazol-5-ylamine | 3528-58-3 | C5H9N3 | 详情 | 详情 |
(III) | 40099 | diethyl 2-[[(1-ethyl-1H-pyrazol-5-yl)amino]methylene]malonate | C13H19N3O4 | 详情 | 详情 | |
(IV) | 40100 | ethyl 1-ethyl-4-hydroxy-1H-pyrazolo[3,4-b]pyridine-5-carboxylate | C11H13N3O3 | 详情 | 详情 | |
(V) | 58542 | ethyl 4-chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate | C11H12ClN3O2 | 详情 | 详情 | |
(VI) | 58543 | ethyl 4-cyano-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate | C12H12N4O2 | 详情 | 详情 | |
(VII) | 58544 | 9-amino-3-ethyl-3,7-dihydro-6H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-one | C10H10N6O | 详情 | 详情 | |
(VIII) | 58545 | 3-ethyl-7,8-dihydro-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine-6,9-dione | C10H9N5O2 | 详情 | 详情 | |
(IX) | 58546 | 6,9-dichloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine | C10H7Cl2N5 | 详情 | 详情 | |
(X) | 58547 | N-methyl-1H-imidazole-4-carboxamide | C5H7N3O | 详情 | 详情 | |
(XI) | 58548 | 1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide | C15H13ClN8O | 详情 | 详情 |