Minamestane, FCE-24928

米那美坦Chemical Name: 4-Aminoandrosta-1,4,6-triene-3,17-dione
CAS No. 105051-87-4
项目整合开发状态: Phase I
项目研究机构: Pfizer (Originator)
合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).
📌 参考资料/链接:
参考文献标题:Process for the preparation of 4-amino-androstenedione derivs
文献作者:(Microbial Chemistry Research Foundation)
参考来源:JP 1984186996

📄 详细内容


合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).

参考文献标题:4-Substd.androst-4-en-3,17-dione derivs.useful as aromatase inhibitors and their manufacturing
文献作者:Faustini,F.; D'Alessio,R.; Villa,V.; Di Salle,E.; Lombardi,P.(Pharmacia Corp.)
参考来源:AU 8653433; BE 0904226; CH 669199; DE 3604179; ES 8706165; ES 8708235; FR 2577556; GB 2171100; JP 1986189295


合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).

参考文献标题:Synthesis of novel 4-aminoandrostenediones
文献作者:Colombo,M.; Longo,A.; Lombardi,P.; Orzi,F.
参考来源:7th IUPAC Conf Org Synth (July 4-7,Nancy) 1988,Abst 7-R7


合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).

参考文献标题:Synthesis and in vitro evaluation of novel aromatase inhibitors
文献作者:Lombardi,P.; DiSalle,E.; D'Alessio,R.; Faustini,F.; Villa,V.
参考来源:J Steroid Biochem 1986,25(suppl)(Suppl.),Abst 128


合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).

参考文献标题:Minamestane
文献作者:Prous,J.; Mealy,N.; Castar,J.
参考来源:Drugs Fut 1993,18(6),510


合成路线:This compound can be obtained by three related ways:1) The chlorination of androsta-1,4-diene-3,17-dione (I) with SO2Cl2 in pyridine gives 4-chloroandrosta-1,4-diene-3,17-dione (II),which is brominated with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride yielding the 5-bromo derivative.The reaction of (III) with LiCl and Li2CO3 in hot DMF affords 4-chloroandrosta-1,4,6-triene-3,17-dione (IV),which is finally treated with NH4OH in dioxane at 90 C in a pressure vessel.2) The reaction of 7alpha-acetoxy-6beta-bromoandrosta-1,4-diene-3,17-dione (V) with sodium azide in hot DMF gives 4-azidoandrosta-1,4,6-triene-3,17-dione (VI),which is then reduced with propane-1,3-dithiol and triethylamine in anhydrous methanol.3) The reaction of 6beta,7alpha-dibromoandrosta-1,4-diene-3,17-dione (VII) with sodium azide as before also yields the azido derivative (VI).
参考文献标题:Synthesis of novel aromatase inhibitors from bromosteroidal intermediates
文献作者:Colombo,M.; Longo,A.; Orzi,F.; Buzzetti,F.; Lombardi,P.
参考来源:Ind Chem Libr 1991,3119-25


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