合成路线:The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II),which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV).The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V).This nitroamine can also be obtained by nitration of 5-aminoindane (I).The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr leads to 6-nitro-5-bromoindane (VI),which reacts with 2,4-difluorophenol in the presence of KOC(CH3)3/CuCl in tert-butanol to yield 6-nitro-5-(2,4-difluorophenoxy)indane (VII).Starting from (VII),CGP-28238 can be prepared by two different routes:a) Condensation of (VII) with tert-butoxy-bis(dimethylamino)methane followed by ozonolysis of the enamine (VIII),and reduction of the nitro group using Raney-Ni and hydrazine hydrate yields 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X).In the last step the intermediate (X) is mesylated with mesylchloride to give CGP-28238.b) Reduction of (VII) using Raney-Ni and hydrazine hydrate gives 5-amino-6-(2,4-difluorophenoxy)indane (XI),which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanone (XII) and (XIII).Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X),which can be mesylated,as before,to CGP-28238.
合成路线:A) Synthesis of intermediate (VII):The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II),which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV).The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V).This nitroamine can also be obtained by nitration of 5-aminoindane (I).The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr gives 6-nitro-5-bromoindane (VI),which reacts with phenol in the presence of either K2CO3/ CuCl in pyridine (Method A) or t-BuOK in DMF (Method B) or t-BuOK/CuCl in tert-butanol (Method C) to yield 6-nitro-5-phenoxyindane (VII).
合成路线:1) Condensation of (VII) with tert-butoxybis(dimethylamino)methane followed by ozonolysis of the enamine (VIII) and reduction of the nitro group using Raney Ni yields 5-amino-6-phenoxy-1-indanone (X).In the last step the intermediate (X) is mesylated with mesyl chloride to give CGP 28237.
合成路线:2) Reduction of (VII) using Raney Ni gives 5-amino-6-phenoxyindane (XI),which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanones (XII) and (XIII).Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-phenoxy-1-indanone (X),which can be mesylated,as before,to CGP-28237.
参考文献标题:Non-steroidal antiinflammatory compounds.6.Antii
文献作者:Schr鰀er,E.; Lehmann,M.; Rufer,C.; B鰐tcher,I.
参考来源:Eur J Med Chem 1982,17(1),35-42
合成路线:The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II),which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV).The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V).This nitroamine can also be obtained by nitration of 5-aminoindane (I).The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr leads to 6-nitro-5-bromoindane (VI),which reacts with 2,4-difluorophenol in the presence of KOC(CH3)3/CuCl in tert-butanol to yield 6-nitro-5-(2,4-difluorophenoxy)indane (VII).Starting from (VII),CGP-28238 can be prepared by two different routes:a) Condensation of (VII) with tert-butoxy-bis(dimethylamino)methane followed by ozonolysis of the enamine (VIII),and reduction of the nitro group using Raney-Ni and hydrazine hydrate yields 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X).In the last step the intermediate (X) is mesylated with mesylchloride to give CGP-28238.b) Reduction of (VII) using Raney-Ni and hydrazine hydrate gives 5-amino-6-(2,4-difluorophenoxy)indane (XI),which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanone (XII) and (XIII).Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X),which can be mesylated,as before,to CGP-28238.
合成路线:A) Synthesis of intermediate (VII):The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II),which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV).The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V).This nitroamine can also be obtained by nitration of 5-aminoindane (I).The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr gives 6-nitro-5-bromoindane (VI),which reacts with phenol in the presence of either K2CO3/ CuCl in pyridine (Method A) or t-BuOK in DMF (Method B) or t-BuOK/CuCl in tert-butanol (Method C) to yield 6-nitro-5-phenoxyindane (VII).
合成路线:1) Condensation of (VII) with tert-butoxybis(dimethylamino)methane followed by ozonolysis of the enamine (VIII) and reduction of the nitro group using Raney Ni yields 5-amino-6-phenoxy-1-indanone (X).In the last step the intermediate (X) is mesylated with mesyl chloride to give CGP 28237.
合成路线:2) Reduction of (VII) using Raney Ni gives 5-amino-6-phenoxyindane (XI),which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanones (XII) and (XIII).Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-phenoxy-1-indanone (X),which can be mesylated,as before,to CGP-28237.
参考文献标题:Non-steroidal antiinflammatory compounds.8.Antii
文献作者:Rufer,C.; Bahlmann,F.; Schr鰀er,E.; B鰐tcher,I.
参考来源:Eur J Med Chem 1982,17(1),173-80
合成路线:The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II),which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV).The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V).This nitroamine can also be obtained by nitration of 5-aminoindane (I).The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr leads to 6-nitro-5-bromoindane (VI),which reacts with 2,4-difluorophenol in the presence of KOC(CH3)3/CuCl in tert-butanol to yield 6-nitro-5-(2,4-difluorophenoxy)indane (VII).Starting from (VII),CGP-28238 can be prepared by two different routes:a) Condensation of (VII) with tert-butoxy-bis(dimethylamino)methane followed by ozonolysis of the enamine (VIII),and reduction of the nitro group using Raney-Ni and hydrazine hydrate yields 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X).In the last step the intermediate (X) is mesylated with mesylchloride to give CGP-28238.b) Reduction of (VII) using Raney-Ni and hydrazine hydrate gives 5-amino-6-(2,4-difluorophenoxy)indane (XI),which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanone (XII) and (XIII).Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X),which can be mesylated,as before,to CGP-28238.
参考文献标题:CGP-28238
文献作者:Wiesenberg,I.; Ferrini,P.G.
参考来源:Drugs Fut 1989,14(11),1035
产品链接: CAS No. 80937-31-1››