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Bemoradan, RWJ-22867, Orf-22867

2H-1,4-苯并嗪-3(4H)-酮,7-(1,4,5,6-四氢-4-甲基-6-氧-3-吡啶达肼)- 贝莫拉旦 Chemical Name: (?-5-Methyl-6-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2,3,4,5-tetrahydropyridazin-3-one; (?-7-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-2H-1,4-benzoxazin-3(4H)-one
CAS No. 123169-88-0, 112018-01-6 (undefined stereoch.)
项目整合开发状态: Phase II
项目研究机构: Ortho-McNeil (Originator)
合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.
📌 参考资料/链接:
参考文献标题:Bemoradan and related pyridazinone cardiotonics
文献作者:Combs,D.W.
参考来源:Drugs Fut 1993,18(2),139

📄 详细内容


合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.

参考文献标题:Electrophilic substitutions of 2H-1,4-benzoxazine-3-one: Acylation and chlorosulfonation
文献作者:Kryvenko,M.; Techer,H.; Lavergne,M.; et al.
参考来源:CR Acad Sci Paris Ser C 1970,270(19),1601


合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.

参考文献标题:6-Acyl benzoxazolinones.I
文献作者:Bonte,J.P.; Lesier,D.; Lespagnol,C.; et al.
参考来源:Eur J Med Chem - Chim Ther 1974,9491


合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.

参考文献标题:6-Acyl benzoxazolinones.II.Preparation of some transformation products
文献作者:Lesier,D.; Lespagnol,C.; Bonte,J.P.; et al.
参考来源:Eur J Med Chem - Chim Ther 1974,9497-500


合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.

参考文献标题:6-Aryl-4,5-dihydro-3(2H)-pyridazinones.A new class of compounds with platelet aggregation inhibiting and hypotensive activities
文献作者:Thyes,M.; Lehmann,H.D.; Gries,J.; et al.
参考来源:J Med Chem 1983,26(6),800


合成路线:The acylation of benzoxazolin-2-one (I) with propionic anhydride (II) by means of P2O5 and MsOH gives 6-propionylbenzoxazolin-2-one (III),which is treated with chloroacetyl chloride to yield 7-propionyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (IV).The Mannich condensation of (IV) with CH2O and NH3 followed by methylation with methyl iodide affords the trimethylammonium compound (V),which by reaction with KCN,followed by hydrolysis with HCl gives 3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarbonyl)butyric acid (VI).Finally this compound is cyclized with hydrazine to furnish the target pyridazinone.
参考文献标题:An aternative synthesis of cardiotonic 6-(3,4-dihydro-3-oxo-1,4[2H]benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-ones
文献作者:Moussavi,Z.; Lesieur,D.; Depreux,P.
参考来源:Synth Commun 1991,21(2),271


产品链接: CAS No. 123169-88-0››

产品链接: CAS No.112018-01-6››