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【结 构 式】 
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【分子编号】52617 【品名】4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-amine; 4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-ylamine 【CA登记号】 |
【 分 子 式 】C11H11Cl2N3O 【 分 子 量 】272.13336 【元素组成】C 48.55% H 4.07% Cl 26.06% N 15.44% O 5.88% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2,6-dichloro-4-methoxybenzyl chloride (I) with tetraethylammonium cyanide in refluxing dichloromethane gives 2-(2,6-dichloro-4-methoxyphenyl)acetonitrile (II), which is condensed with ethyl acetate (III) by means of sodium ethoxide in refluxing ethanol to yield the 3-oxobutyronitrile (IV). The cyclization of (IV) with hydrazine (V) by means of HOAc in refluxing benzene affords the aminopyrazole (VI), which is further cyclized with ethyl acetoacetate (VII) in refluxing acetic acid to provide 3-(2,6-dichloro-4-methoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol (VIII). The reaction of (VIII) with refluxing POCl3 furnishes the corresponding chloro derivative (IX), which is allowed to react with ethylenediamine (X) in hot acetonitrile to give 7-(2-aminoethylamino)-3-(2,6-dichloro-4-methoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine (XI). Finally, this compound is reductocondensed with tetrahydropyran-4-one (XII) by means of sodium cyanoborohydride in methanol/HOAc to yield the target CP-671906-01.
| 【1】 Giangiordano, M.; Tran, J.; Darrow, J.W.; De Lombaert, S.; Blum, C.; Griffith, D.A.; Carpino, P.A. (Neurogen Corp.; Pfizer Inc.); Certain alkylene diamine-substd. pyrazolo[1,5-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines. US 6372743; WO 0123387 . |
| 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) | 52615 | 3,5-dichloro-4-(chloromethyl)phenyl methyl ether; 1,3-dichloro-2-(chloromethyl)-5-(methyloxy)benzene | C8H7Cl3O | 详情 | 详情 | |
| (II) | 52616 | 2-[2,6-dichloro-4-(methyloxy)phenyl]acetonitrile | C9H7Cl2NO | 详情 | 详情 | |
| (III) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (IV) | 52621 | 2-[2,6-dichloro-4-(methyloxy)phenyl]-3-oxobutanenitrile | C11H9Cl2NO2 | 详情 | 详情 | |
| (V) | 27344 | hydrazine | 302-01-2 | H4N2 | 详情 | 详情 |
| (VI) | 52617 | 4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-amine; 4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-ylamine | C11H11Cl2N3O | 详情 | 详情 | |
| (VII) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (VIII) | 52618 | 3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol | C15H13Cl2N3O2 | 详情 | 详情 | |
| (IX) | 52619 | 7-chloro-3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidine; 3,5-dichloro-4-(7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)phenyl methyl ether | C15H12Cl3N3O | 详情 | 详情 | |
| (X) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (XI) | 52620 | N~1~-{3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl}-1,2-ethanediamine | C17H19Cl2N5O | 详情 | 详情 | |
| (XII) | 31563 | tetrahydro-4H-pyran-4-one | 29943-42-8 | C5H8O2 | 详情 | 详情 |