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Atamestane, Biomed-777, SH-489

阿他美坦Chemical Name: 1-Methylandrosta-1,4-dien-3,17-dione
CAS No. 96301-34-7
项目整合开发状态: Phase III
项目研究机构: Schering AG (Originator), Intarcia (Licensee)
合成路线:This compound can be obtained by three different ways:1) The methylation of androsta-1,4-diene-3,17-dione (I) with methyllithium and Cu2I2,followed by acetylation with acetic anhydride gives 3-acetoxy-1alpha-methylandrosta-2,4-dien-17-one (II),which is treated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) in dioxane - water yielding 2alpha(beta)-bromo-1alpha-methylandrost-4-ene-3,17-dione (III).Finally,this compound is dehydrobrominated with MgO in hot DMF.2) By oxidation of 17beta-hydroxy-1-methylandrosta-1,4-dien-3-one (IV) with chromium trioxide and H2SO4 in acetone.3) By oxidation of 17beta-hydroxy-1-methylandrost-1-en-3-one (V) with iodoxybenzene and diphenyldiselenide in hot toluene.
📌 参考资料/链接:
参考文献标题:Process for the production of 1-methyl-1,4-androstadien-3,17-dione
文献作者:Petzoldt,K.(Schering AG)
参考来源:WO 8605813

📄 详细内容


合成路线:This compound can be obtained by three different ways:1) The methylation of androsta-1,4-diene-3,17-dione (I) with methyllithium and Cu2I2,followed by acetylation with acetic anhydride gives 3-acetoxy-1alpha-methylandrosta-2,4-dien-17-one (II),which is treated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) in dioxane - water yielding 2alpha(beta)-bromo-1alpha-methylandrost-4-ene-3,17-dione (III).Finally,this compound is dehydrobrominated with MgO in hot DMF.2) By oxidation of 17beta-hydroxy-1-methylandrosta-1,4-dien-3-one (IV) with chromium trioxide and H2SO4 in acetone.3) By oxidation of 17beta-hydroxy-1-methylandrost-1-en-3-one (V) with iodoxybenzene and diphenyldiselenide in hot toluene.

参考文献标题:Process for the preparation of 1-methyl-androsta-1,4-dien-3,17-dione and novel intermediates for this process
文献作者:Nickisch,K.; Arnold,H.(Schering AG)
参考来源:EP 0290378


合成路线:This compound can be obtained by three different ways:1) The methylation of androsta-1,4-diene-3,17-dione (I) with methyllithium and Cu2I2,followed by acetylation with acetic anhydride gives 3-acetoxy-1alpha-methylandrosta-2,4-dien-17-one (II),which is treated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) in dioxane - water yielding 2alpha(beta)-bromo-1alpha-methylandrost-4-ene-3,17-dione (III).Finally,this compound is dehydrobrominated with MgO in hot DMF.2) By oxidation of 17beta-hydroxy-1-methylandrosta-1,4-dien-3-one (IV) with chromium trioxide and H2SO4 in acetone.3) By oxidation of 17beta-hydroxy-1-methylandrost-1-en-3-one (V) with iodoxybenzene and diphenyldiselenide in hot toluene.

合成路线:FK-352 can be obtained by two related ways:1) The Wittig condensation of 2-phenylpyrazolo[1,5-a]pyridine-3-carbaldehyde (I) with trimethyl phosphonoacetate (II) by means of NaH in hot toluene gives 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2(E)-propenoic acid methyl ester (III),which by hydrolysis with aqueous NaOH yields the expected free acid (IV) (1).The reaction of (IV) with SOCl2 and DMF in dichloromethane affords the corresponding acyl chloride (V),which is condensed with 2-[2(R)-piperidinyl]acetic acid ethyl ester (VI) by means of triethylamine in dichloromethane affording the acylated piperidine (VII).Finally,this compound is hydrolyzed with NaOH in refluxing methanol.2) The free acid precursor (IV) can also be obtained by condensation of 2-phenylpyrazolo[1,5-a]pyridine (VIII) with 3-(dimethylamino)acrylic acid ethyl ester (IX) by means of AlCl3 in methylene chloride giving the ethyl ester (X),which is hydrolyzed to the free acid (IV) by treatment with aqueous NaOH.

参考文献标题:Use of adenosine antagonists in the prevention and treatment of pancreatitis and ulcer
文献作者:Shiokawa,Y.; Akahane,A.; Katayama,H.; Mitsunaga,T.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0497258; JP 1992244084; JP 1993058913; US 5338743


合成路线:This compound can be obtained by three different ways:1) The methylation of androsta-1,4-diene-3,17-dione (I) with methyllithium and Cu2I2,followed by acetylation with acetic anhydride gives 3-acetoxy-1alpha-methylandrosta-2,4-dien-17-one (II),which is treated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) in dioxane - water yielding 2alpha(beta)-bromo-1alpha-methylandrost-4-ene-3,17-dione (III).Finally,this compound is dehydrobrominated with MgO in hot DMF.2) By oxidation of 17beta-hydroxy-1-methylandrosta-1,4-dien-3-one (IV) with chromium trioxide and H2SO4 in acetone.3) By oxidation of 17beta-hydroxy-1-methylandrost-1-en-3-one (V) with iodoxybenzene and diphenyldiselenide in hot toluene.

参考文献标题:Atamestane
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1992,17(10),867


合成路线:This compound can be obtained by three different ways:1) The methylation of androsta-1,4-diene-3,17-dione (I) with methyllithium and Cu2I2,followed by acetylation with acetic anhydride gives 3-acetoxy-1alpha-methylandrosta-2,4-dien-17-one (II),which is treated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) in dioxane - water yielding 2alpha(beta)-bromo-1alpha-methylandrost-4-ene-3,17-dione (III).Finally,this compound is dehydrobrominated with MgO in hot DMF.2) By oxidation of 17beta-hydroxy-1-methylandrosta-1,4-dien-3-one (IV) with chromium trioxide and H2SO4 in acetone.3) By oxidation of 17beta-hydroxy-1-methylandrost-1-en-3-one (V) with iodoxybenzene and diphenyldiselenide in hot toluene.
参考文献标题:Regioselective synthesis of ring.A polymethylated steroids in the androstane series
文献作者:Sauer,G.; K黱zer,H.; Wiechert,R.
参考来源:Tetrahedron 1989,45(20),6409


产品链接: CAS No. 96301-34-7››