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【结 构 式】 
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【药物名称】DPC-696, SK-696, DMP-696 【化学名称】8-(2,4-Dichlorophenyl)-N-[2-methoxy-1-(methoxymethyl)ethyl]-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine 【CA登记号】202578-52-7 【 分 子 式 】C18H21Cl2N5O2 【 分 子 量 】410.30637 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, CRF1 Antagonists |
合成路线1
Claisen condensation of 2,4-dichlorophenylacetonitrile (I) with ethyl acetate using of Na metal gave ketonitrile (II), which was reacted with hydrazine hydrate in the presence of AcOH to afford aminopyrazole (III). Subsequent condensation of (III) with ethyl acetimidate (IV) produced amidine (V). This was cyclized with diethyl carbonate and NaOEt to furnish the pyrazolotriazinone (VI). Chlorination of (VI) using phosphoryl chloride in N,N-dimethylaniline provided chloride (VII), which was finally coupled with 1,3-dimethoxy-2-aminopropane (VIII) to yield the title compound.
| 【1】 Gilligan, P.J.; He, L.; Zaczek, R.; et al.; 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: A potent, orally bioavailable CRF1 receptor antagonist. J Med Chem 2000, 43, 3, 449. |
| 【2】 Arvanitis, A.G.; Chorvat, R.J. (DuPont Pharmaceuticals Co.); Azolo triazines and pyrimidines. US 6124289; WO 9803510 . |
| 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) | 28484 | 2,4.Dichlorobenzyl cyanide; 2-(2,4-Dichlorophenyl)acetonitrile | 6306-60-1 | C8H5Cl2N | 详情 | 详情 |
| (II) | 28485 | 2-(2,4-dichlorophenyl)-3-oxobutanenitrile | C10H7Cl2NO | 详情 | 详情 | |
| (III) | 27688 | 4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine | C10H9Cl2N3 | 详情 | 详情 | |
| (IV) | 12831 | ethyl ethanimidoate | 1000-84-6 | C4H9NO | 详情 | 详情 |
| (V) | 28486 | N-[4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-yl]ethanimidamide | C12H12Cl2N4 | 详情 | 详情 | |
| (VI) | 28487 | 8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4(3H)-one | C13H10Cl2N4O | 详情 | 详情 | |
| (VII) | 28488 | 4-chloro-8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazine | C13H9Cl3N4 | 详情 | 详情 | |
| (VIII) | 23336 | 1,3-dimethoxy-2-propanamine | C5H13NO2 | 详情 | 详情 |