CI-943

1H-伊咪唑[1,2-c]吡嘧唑[3,4-e]嘧啶,8-乙基-7,8-二氢-1,3,5-三甲基- Chemical Name: 8-Ethyl-1,3,5-trimethyl-7,8-dihydro-1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine
CAS No. 111770-15-1 (racemate), 89239-35-0 (undefined stereoch.)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:The cyclization of 4-amino-1,3-dimethyl-1H-pyrazole-5-carbonitrile (I) or 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxamide (II) with acetic anhydride and H2O2 or NaOH gives 1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidin-7-one (III),which by reaction with POCl3/PCl3 is converted into 7-chloro-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (IV).The reaction of (IV) with 2-ethylaziridine (V) affords 7-(2-ethylaziridin-1-yl)-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (VI),which is finally rearranged to the tricyclic target compound by means of NaI in acetone.

合成路线:The reaction of 1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one (I) with POCl3 followed by nitration with HNO3 gives 5-chloro-1,3-dimethyl-4-nitro-1H-pyrazole (II),which is treated with KCN to yield 1,3-dimethyl-4-nitro-1H-pyrazole-5-carbonitrile (III).The cyclization of (III) with butane-1,2-diamine (IV) by means of Ts-OH affords the imidazoline (V),which is acylated with acetic anhydride to provide the 1-acetyl imidazoline (VI).Finally,this compound is cyclized by reduction of its NO2 group followed by heating.
📌 参考资料/链接:
参考文献标题:The potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines
文献作者:Wise,L.D.; Heffner,T.G.
参考来源:Drugs Fut 1989,14(11),1073

📄 详细内容


合成路线:The cyclization of 4-amino-1,3-dimethyl-1H-pyrazole-5-carbonitrile (I) or 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxamide (II) with acetic anhydride and H2O2 or NaOH gives 1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidin-7-one (III),which by reaction with POCl3/PCl3 is converted into 7-chloro-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (IV).The reaction of (IV) with 2-ethylaziridine (V) affords 7-(2-ethylaziridin-1-yl)-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (VI),which is finally rearranged to the tricyclic target compound by means of NaI in acetone.

合成路线:The reaction of 1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one (I) with POCl3 followed by nitration with HNO3 gives 5-chloro-1,3-dimethyl-4-nitro-1H-pyrazole (II),which is treated with KCN to yield 1,3-dimethyl-4-nitro-1H-pyrazole-5-carbonitrile (III).The cyclization of (III) with butane-1,2-diamine (IV) by means of Ts-OH affords the imidazoline (V),which is acylated with acetic anhydride to provide the 1-acetyl imidazoline (VI).Finally,this compound is cyclized by reduction of its NO2 group followed by heating.

参考文献标题:Synthesis and potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines
文献作者:Beeson,N.W.; Pugsley,T.A.; Coughenour,L.L.; Hershenson,F.; Heffner,T.G.; Downs,D.A.; Wise,L.D.; DeWald,H.A.
参考来源:J Med Chem 1988,31454-460


合成路线:The cyclization of 4-amino-1,3-dimethyl-1H-pyrazole-5-carbonitrile (I) or 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxamide (II) with acetic anhydride and H2O2 or NaOH gives 1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidin-7-one (III),which by reaction with POCl3/PCl3 is converted into 7-chloro-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (IV).The reaction of (IV) with 2-ethylaziridine (V) affords 7-(2-ethylaziridin-1-yl)-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (VI),which is finally rearranged to the tricyclic target compound by means of NaI in acetone.

合成路线:The reaction of 1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one (I) with POCl3 followed by nitration with HNO3 gives 5-chloro-1,3-dimethyl-4-nitro-1H-pyrazole (II),which is treated with KCN to yield 1,3-dimethyl-4-nitro-1H-pyrazole-5-carbonitrile (III).The cyclization of (III) with butane-1,2-diamine (IV) by means of Ts-OH affords the imidazoline (V),which is acylated with acetic anhydride to provide the 1-acetyl imidazoline (VI).Finally,this compound is cyclized by reduction of its NO2 group followed by heating.

参考文献标题:Synthesis and structure-activity relationships of pyrazolo[4,3-d]pyrimidin-7-ones as adenosine receptor antagonists
文献作者:Bristol,J.A.; Hamilton,H.W.; Worth,D.F.; Ortwine,D.F.
参考来源:J Med Chem 1987,3091-96


合成路线:The cyclization of 4-amino-1,3-dimethyl-1H-pyrazole-5-carbonitrile (I) or 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxamide (II) with acetic anhydride and H2O2 or NaOH gives 1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidin-7-one (III),which by reaction with POCl3/PCl3 is converted into 7-chloro-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (IV).The reaction of (IV) with 2-ethylaziridine (V) affords 7-(2-ethylaziridin-1-yl)-1,3,5-trimethyl-6,7-dihydro-1H-pyrazolo[4,5-d]pyrimidine (VI),which is finally rearranged to the tricyclic target compound by means of NaI in acetone.
参考文献标题:Potential purine antagonists.VII.Synthesis of 6-alkylpyrazolo[3,4-d]pyrimidines
文献作者:Cheng,C.C.; Robins,R.K.
参考来源:J Org Chem 1958,23191-200


产品链接: CAS No.89239-35-0››