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【结 构 式】 
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【药物名称】CV-159 【化学名称】1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester 【CA登记号】86384-98-7 【 分 子 式 】C31H34N4O7 【 分 子 量 】574.63923 |
【开发单位】Mitsubishi Pharma (Originator) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Calcium Channel Blockers |
合成路线1
Reaction of 6-chlorohexanol (I) with 3-phenyl-5-pyrazolone (II) in the presence of K2CO3 in DMF gives 6-(5-phenyl-3-pyrazolyloxy)hexyl alcohol (III), which affords the crystalline acetoacetate derivative (IV) by esterification of (III) with diketene in the presence of triethylamine. Reaction of (IV) and ammonium carbonate in refluxing methanol gives 3-aminocrotonic acid 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (V). This compound is finally cyclized with methyl 3-nitrobenzylidene acetoacetate (VI) in ethanol.
| 【1】 Masato, K.; Shinji, T.; Kozo, H.; Susumu, T. (Tokyo Tanabe Co., Ltd.); Novel 1,4-dihydropyridine derivatives. DE 3230400; FR 2511370; FR 8214008; GB 2108108; JP 88023193; US 4418197 . |
| 【2】 Masato, K.; Shinji, T.; Tsutomu, A.; Setagaya, S.C.; Susumu, T. (Tokyo Tanabe Co., Ltd.); Powdery preparation of amorphous dihydropyridine compound. EP 0147171; JP 60139688 . |
| 【3】 Kamibayashi, M.; CV-159. Drugs Fut 1989, 14, 3, 206. |
| 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) | 20513 | 6-chloro-1-hexanol | 2009-83-8 | C6H13ClO | 详情 | 详情 |
| (II) | 20514 | 5-phenyl-2,4-dihydro-3H-pyrazol-3-one | C9H8N2O | 详情 | 详情 | |
| (III) | 20515 | 6-[(5-phenyl-1H-pyrazol-3-yl)oxy]-1-hexanol | C15H20N2O2 | 详情 | 详情 | |
| (IV) | 20516 | 6-[(5-phenyl-1H-pyrazol-3-yl)oxy]hexyl 3-amino-3-oxopropanoate | C18H23N3O4 | 详情 | 详情 | |
| (V) | 20517 | 6-[(5-phenyl-1H-pyrazol-3-yl)oxy]hexyl (E)-3-amino-2-butenoate | C19H25N3O3 | 详情 | 详情 | |
| (VI) | 12276 | methyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C12H11NO5 | 详情 | 详情 | |
| (VII) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |