合成路线:The reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III),which is protected with benzyl chloroformate (IV) and TEA,yielding dicarbamate (V).Selective deprotection of (V) with dry HCl in ethyl acetate affords the primary amine (VI),which is treated with 3(S)-tetrahydrofuryl N-succinimidinyl carbonate (VII) -- obtained by reaction of tetrahydrofuran-3(S)-ol (VIII) first with phosgene and then with N-hydroxysuccinimide (IX) -- and DIEA in acetonitrile to provide the corresponding carbamate (X).Deprotection of (X) by hydrogenation with H2 over Pd/C in ethanol gives the secondary amine (XI),which is condensed with 4-nitrophenylsulfonyl chloride (XII) by means of NaHCO3 in dichloromethane/water to yield the sulfonamide intermediate (XIII).
参考文献标题:THF-containing sulfonamide inhibitors of aspartyl protease
文献作者:Tung,R.D.(Vertex Pharmaceuticals Inc.)
参考来源:EP 0846110; WO 9633184
合成路线:Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII),which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII).Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX).Finally,fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts.Alternatively,the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine,followed by hydrolysis with 2N HCl.
参考文献标题:Sulphonamide derivs.as prodrugs of aspartyl protease inhibitors
文献作者:Kazmierski,W.W.; Hale,M.R.; Tung,R.D.; Furfine,E.S.; Kaldor,I.; Baker,C.T.; Spaltenstein,A.(Vertex Pharmaceuticals Inc.)
参考来源:CA 2231700; EP 0933372; JP 1999209337; WO 9933815
合成路线:Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII),which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII).Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX).Finally,fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts.Alternatively,the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine,followed by hydrolysis with 2N HCl.
参考文献标题:Prodrugs of aspartyl protease inhibitors
文献作者:Kaldor,I.; Hale,M.R.; Furfine,E.S.; Baker,C.T.; Tung,R.D.; Kazmierski,W.M.; Spaltenstein,A.(Vertex Pharmaceuticals Inc.)
参考来源:WO 9933792
合成路线:Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII),which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII).Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX).Finally,fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts.Alternatively,the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine,followed by hydrolysis with 2N HCl.
参考文献标题:Prodrugs of aspartyl protease inhibitors
文献作者:Spaltenstein,A.; Kazmierski,W.M.; Kaldor,I.; Baker,C.T.; Hale,M.R.; Tung,R.D.; Furfine,E.S.(Vertex Pharmaceuticals Inc.)
参考来源:WO 9933793
合成路线:Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII),which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII).Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX).Finally,fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts.Alternatively,the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine,followed by hydrolysis with 2N HCl.
参考文献标题:Calcium (3S) tetrahydro-3-furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate
文献作者:Armitage,I.G.; Singh,H.; Searle,A.D.(Glaxo Group Ltd.)
参考来源:WO 0004033
合成路线:Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII),which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII).Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX).Finally,fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts.Alternatively,the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine,followed by hydrolysis with 2N HCl.
参考文献标题:Derivs.of (3S) tetrahydro-3-furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate
文献作者:Crawley,K.; Searle,A.D.(Glaxo Group Ltd.)
参考来源:WO 0100635
产品链接: CAS No. 226700-80-7›› 产品链接: CAS No.226700-79-4››