BOF-4272
Chemical Name: (?-8-[3-Methoxy-4-(phenylsulfinyl)phenyl]pyrazolo[1,5-a]-1,3,5-triazin-4-ol sodium salt hydrate
CAS No. 134395-51-0 ((-)-enantiomer, anhydrous), 134395-58-7 ((-)-enantiomer, Ca salt, anhydrous), 134395-49-6 ((-)-enantiomer, free acid, anhydrous), 134395-57-6 ((-)-enantiomer, K salt, anhydrous), 134395-56-5 ((-)-enantiomer, Li salt, anhydrous), 134395-52-1 (
项目整合开发状态: Phase I
项目研究机构: Otsuka (Originator)
合成路线:The reduction of 3-methoxy-4-(phenylthio)benzoic acid methyl ester (I) with LiAlH4 in ether gives 3-methoxy-4-(phenylthio)benzyl alcohol (II),which by reaction with SOCl2 in dichloromethane yields the corresponding benzyl chloride (III).The reaction of (III) with NaCN in DMF affords 3-methoxy-4-(phenylthio)phenylacetonitrile (IV),which by reaction with ethylformate by means of sodium methoxide in benzene gives 2-formyl-2-[3-methoxy-4-(phenylthio)phenyl]acetonitrile (V).The cyclization of (V) with semicarbazide in methanol - water yields 3-amino-4-[3-methoxy-4-(phenylthio)phenyl]pyrazole-2-carboxamide (VI),which is submitted to a new cyclization process with ethyl orthoformate at 110 C,affording 8-[3-methoxy-4-(phenylthio)phenyl]pyrazolo[1,5-a]-1,3,5-triazine (VII).Finally,this compound is oxidized with sodium metaperiodate in methanol - water.When the oxidation of (VII) is performed with tert-butyl hypochlorite in l-(-)-menthol and pyridine and cooled at -25 to -30 C,the (-)-BOF-4272 isomer is obtained; with d-(+)-menthol,the (+)-BOF-4272 is also obtained.
📌 参考资料/链接：
参考文献标题:Pyrazolotriazine cpds
文献作者:Fujii,S.; Kawamura,H.; Kiyokawa,H.; Yamada,S.(Otsuka Pharmaceutical Co.,Ltd.)
参考来源:EP 0269859; JP 1989079184; JP 1994316578; US 4824834
📄 详细内容
合成路线:The reduction of 3-methoxy-4-(phenylthio)benzoic acid methyl ester (I) with LiAlH4 in ether gives 3-methoxy-4-(phenylthio)benzyl alcohol (II),which by reaction with SOCl2 in dichloromethane yields the corresponding benzyl chloride (III).The reaction of (III) with NaCN in DMF affords 3-methoxy-4-(phenylthio)phenylacetonitrile (IV),which by reaction with ethylformate by means of sodium methoxide in benzene gives 2-formyl-2-[3-methoxy-4-(phenylthio)phenyl]acetonitrile (V).The cyclization of (V) with semicarbazide in methanol - water yields 3-amino-4-[3-methoxy-4-(phenylthio)phenyl]pyrazole-2-carboxamide (VI),which is submitted to a new cyclization process with ethyl orthoformate at 110 C,affording 8-[3-methoxy-4-(phenylthio)phenyl]pyrazolo[1,5-a]-1,3,5-triazine (VII).Finally,this compound is oxidized with sodium metaperiodate in methanol - water.When the oxidation of (VII) is performed with tert-butyl hypochlorite in l-(-)-menthol and pyridine and cooled at -25 to -30 C,the (-)-BOF-4272 isomer is obtained; with d-(+)-menthol,the (+)-BOF-4272 is also obtained.
参考文献标题:Salts of optically active 4-hydroxy-8-(3-lower alkoxy-4-phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5-triazines and process for production thereof
文献作者:Hashimoto,K.; Inai,M.(Otsuka Pharmaceutical Co.,Ltd.)
参考来源:AU 9160985; EP 0414200; JP 1991163082; US 5137887
合成路线:The reduction of 3-methoxy-4-(phenylthio)benzoic acid methyl ester (I) with LiAlH4 in ether gives 3-methoxy-4-(phenylthio)benzyl alcohol (II),which by reaction with SOCl2 in dichloromethane yields the corresponding benzyl chloride (III).The reaction of (III) with NaCN in DMF affords 3-methoxy-4-(phenylthio)phenylacetonitrile (IV),which by reaction with ethylformate by means of sodium methoxide in benzene gives 2-formyl-2-[3-methoxy-4-(phenylthio)phenyl]acetonitrile (V).The cyclization of (V) with semicarbazide in methanol - water yields 3-amino-4-[3-methoxy-4-(phenylthio)phenyl]pyrazole-2-carboxamide (VI),which is submitted to a new cyclization process with ethyl orthoformate at 110 C,affording 8-[3-methoxy-4-(phenylthio)phenyl]pyrazolo[1,5-a]-1,3,5-triazine (VII).Finally,this compound is oxidized with sodium metaperiodate in methanol - water.When the oxidation of (VII) is performed with tert-butyl hypochlorite in l-(-)-menthol and pyridine and cooled at -25 to -30 C,the (-)-BOF-4272 isomer is obtained; with d-(+)-menthol,the (+)-BOF-4272 is also obtained.
参考文献标题:BOF-4272
文献作者:Prous,J.; Graul,A.; Castar,J.
参考来源:Drugs Fut 1993,18(9),791