DPC-696, SK-696, DMP-696
Chemical Name: 8-(2,4-Dichlorophenyl)-N-[2-methoxy-1-(methoxymethyl)ethyl]-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine
CAS No. 202578-52-7
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The cyclization of 5-amino-4-(4-methoxy-2-methylphenyl)-3-methylpyrazole with ethyl acetoacetate (II) in refluxing acetic acid gives 7-hydroxy-3-(4-methoxy-2-methylphenyl)-5-methylpyrazolo[1,5-a]pyrimidine (III),which is treated with POCl3 and diethylaniline in refluxing toluene yielding the corresponding chloro derivative (IV).Finally,this compound is treated with pentyl-3-amine in DMSO at 150 C.
合成路线: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.
📌 参考资料/链接：
参考文献标题:Azolo triazines and pyrimidines
文献作者:Arvanitis,A.G.; Chorvat,R.J.(DuPont Pharmaceuticals Co.)
参考来源:US 6124289; WO 9803510
📄 详细内容
合成路线: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.
参考文献标题: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
文献作者:He,L.; Gilligan,P.J.; Zaczek,R.; Fitzgerald,L.W.; McElroy,J.; Shen,H.S.; Saye,J.A.; Kalin,N.H.; Shelton,S.; Christ,D.; Trainor,G.; Hartig,P.
参考来源:J Med Chem 2000,43(3),449
产品链接: CAS No. 202578-52-7››