【药物名称】Atamestane, Biomed-777, SH-489
化学结构式(Chemical Structure):
参考文献No.19069
标题:Process for the production of 1-methyl-1,4-androstadien-3,17-dione
作者:Petzoldt, K. (Schering AG)
来源:WO 8605813
合成路线图解说明:

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No.19070
标题:Process for the preparation of 1-methyl-androsta-1,4-dien-3,17-dione and novel intermediates for this process
作者:Nickisch, K.; Arnold, H. (Schering AG)
来源:EP 0290378
合成路线图解说明:

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No.19192
标题:Use of adenosine antagonists in the prevention and treatment of pancreatitis and ulcer
作者:Shiokawa, Y.; Akahane, A.; Katayama, H.; Mitsunaga, T. (Fujisawa Pharmaceutical Co., Ltd.)
来源:EP 0497258; JP 1992244084; JP 1993058913; US 5338743
合成路线图解说明:

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.

合成路线图解说明:

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No.185843
标题:Atamestane
作者:Prous, J.; Casta馿r, J.
来源:Drugs Fut 1992,17(10),867
合成路线图解说明:

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No.189620
标题:Regioselective synthesis of ring. A polymethylated steroids in the androstane series
作者:Sauer, G.; K黱zer, H.; Wiechert, R.
来源:Tetrahedron 1989,45(20),6409
合成路线图解说明:

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.

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