AP-23317
Chemical Name: [4-[2-(4-Aminocyclohexylamino)-9-ethyl-9H-purin-6-ylamino]phenyl](hydroxy)phosphorylmethyl]phosphonic acid
CAS No. 344585-41-7 (trans-isomer)
项目整合开发状态: Preclinical
项目研究机构: Ariad Pharmaceuticals (Originator)
合成路线:2-Amino-6-chloropurine (I) is converted into the 2-fluoro analogue (II) by diazotization in the presence of fluoroboric acid.Subsequent alkylation of (II) with EtOH under Mitsunobu conditions provides the 9-ethyl purine (III).
合成路线:Reaction of phosphinylmethyl phosphonate (IV) with 1-iodo-4-nitrobenzene (V) in the presence of Pd(PPh3)4 affords the nitrophenyl phosphinoyl derivative (VI).Reduction of the nitro group of (VI) to the corresponding aniline (VII) is accomplished by treatment with SnCl2 in ethanol.Then,hydrolysis of the triethyl ester (VII) under acidic conditions furnishes phosphonic acid (VIII).Displacement of the 6-chloro group of purine (III) with the aminophenyl phosphonic acid (VIII) in hot DMSO gives rise to the 6-anilino purine (IX).Finally,displacement of the remaining halogen atom of (IX) with trans-1,4-diaminocyclohexane (X) leads to the title 2,6-diaminopurine compound.
📌 参考资料/链接：
参考文献标题:Purine derivs.
文献作者:Weigele,M.; Sawyer,T.K.; Wang,Y.; Shakespeare,W.C.; Bohacek,R.; Sundaramoorthi,R.; Metcalf,C.A.III; Dalgarno,D.C.(Ariad Pharmaceuticals Inc.)
参考来源:US 2002068721
📄 详细内容
合成路线:2-Amino-6-chloropurine (I) is converted into the 2-fluoro analogue (II) by diazotization in the presence of fluoroboric acid.Subsequent alkylation of (II) with EtOH under Mitsunobu conditions provides the 9-ethyl purine (III).
合成路线:Reaction of phosphinylmethyl phosphonate (IV) with 1-iodo-4-nitrobenzene (V) in the presence of Pd(PPh3)4 affords the nitrophenyl phosphinoyl derivative (VI).Reduction of the nitro group of (VI) to the corresponding aniline (VII) is accomplished by treatment with SnCl2 in ethanol.Then,hydrolysis of the triethyl ester (VII) under acidic conditions furnishes phosphonic acid (VIII).Displacement of the 6-chloro group of purine (III) with the aminophenyl phosphonic acid (VIII) in hot DMSO gives rise to the 6-anilino purine (IX).Finally,displacement of the remaining halogen atom of (IX) with trans-1,4-diaminocyclohexane (X) leads to the title 2,6-diaminopurine compound.
参考文献标题:Novel purines
文献作者:Weigele,M.; Sawyer,T.K.; Wang,Y.; Shakespeare,W.; Bohacek,R.; Sundaramoorthi,R.; Metcalf,C.A.III (Ariad Pharmaceuticals Inc.)
参考来源:WO 0144260
合成路线:2-Amino-6-chloropurine (I) is converted into the 2-fluoro analogue (II) by diazotization in the presence of fluoroboric acid.Subsequent alkylation of (II) with EtOH under Mitsunobu conditions provides the 9-ethyl purine (III).
合成路线:Reaction of phosphinylmethyl phosphonate (IV) with 1-iodo-4-nitrobenzene (V) in the presence of Pd(PPh3)4 affords the nitrophenyl phosphinoyl derivative (VI).Reduction of the nitro group of (VI) to the corresponding aniline (VII) is accomplished by treatment with SnCl2 in ethanol.Then,hydrolysis of the triethyl ester (VII) under acidic conditions furnishes phosphonic acid (VIII).Displacement of the 6-chloro group of purine (III) with the aminophenyl phosphonic acid (VIII) in hot DMSO gives rise to the 6-anilino purine (IX).Finally,displacement of the remaining halogen atom of (IX) with trans-1,4-diaminocyclohexane (X) leads to the title 2,6-diaminopurine compound.
参考文献标题:Purine derivs.
文献作者:Weigele,M.; Sawyer,T.K.; Wang,Y.; Shakespeare,W.C.; Bohacek,R.; Sundaramoorthi,R.; Metcalf,C.A.III; Dalgarno,D.C.(Ariad Pharmaceuticals Inc.)
参考来源:WO 0144259