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【结 构 式】 
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【药物名称】NIDA-41020 【化学名称】1-(2,4-Dichlorophenyl)-5-(4-methoxyphenyl)-4-methyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide 【CA登记号】 【 分 子 式 】C23H24Cl2N4O2 【 分 子 量 】459.37933 |
【开发单位】National Institute on Drug Abuse (Originator) 【药理作用】DIAGNOSTIC AGENTS, Radiopharmaceuticals, Radiopharmaceuticals for Brain Imaging, Cannabinoid CB1 Antagonists |
合成路线1
Claisen condensation of the lithium enolate of 4-methoxypropiophenone (I) with diethyl oxalate leads to diketo ester (II). Treatment of (II) with 2,4-dichlorophenyl hydrazine (III), followed by cyclization of the resultant hydrazone (IV) in boiling AcOH furnishes the pyrazolecarboxylate (V). Alkaline hydrolysis of ester (V) yields carboxylic acid (VI), which is further activated as the acid chloride (VII) with SOCl2 in refluxing toluene. Finally, coupling of acid chloride (VII) with 1-aminopiperidine (VIII) produces the target hydrazide derivative.
| 【1】 Katoch-Rouse, R.; Pavlova, O.A.; Caulder, T.; Hoffman, A.F.; Mukhin, A.G.; Horti, A.G.; Synthesis, structure-activity relationship, and evaluation of SR141716 analogues: Development of central cannabinoid receptor ligands with lower lipophilicity. J Med Chem 2003, 46, 4, 642. |
| 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) | 64383 | 1-[4-(methyloxy)phenyl]-1-propanone | C10H12O2 | 详情 | 详情 | |
| (II) | 64384 | ethyl 3-methyl-4-[4-(methyloxy)phenyl]-2,4-dioxobutanoate | C14H16O5 | 详情 | 详情 | |
| (III) | 35778 | 1-(2,4-dichlorophenyl)hydrazine | 5446-18-4 | C6H6Cl2N2 | 详情 | 详情 |
| (IV) | 64385 | ethyl 2-[2-(2,4-dichlorophenyl)hydrazono]-3-methyl-4-[4-(methyloxy)phenyl]-4-oxobutanoate | C20H20Cl2N2O4 | 详情 | 详情 | |
| (V) | 64386 | ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-[4-(methyloxy)phenyl]-1H-pyrazole-3-carboxylate | C20H18Cl2N2O3 | 详情 | 详情 | |
| (VI) | 64387 | 1-(2,4-dichlorophenyl)-4-methyl-5-[4-(methyloxy)phenyl]-1H-pyrazole-3-carboxylic acid | C18H14Cl2N2O3 | 详情 | 详情 | |
| (VII) | 64388 | 1-(2,4-dichlorophenyl)-4-methyl-5-[4-(methyloxy)phenyl]-1H-pyrazole-3-carbonyl chloride | C18H13Cl3N2O2 | 详情 | 详情 | |
| (VIII) | 35781 | 1-piperidinylamine; 1-piperidinamine | 2213-43-6 | C5H12N2 | 详情 | 详情 |