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项目整合精选>>>Roxifiban acetate, SC-887(mesylate), DMP-755(free base), XU-070(HCl), DMP-754, Lumaxis
Roxifiban acetate, SC-887(mesylate), DMP-755(free base), XU-070(HCl), DMP-754, Lumaxis
罗昔非班乙酸盐 L-丙氨酸,3-[[2-[(5R)-3-[4-(氨基亚氨基甲基)苯基]-4,5-二氢-5-is氧唑基乙酰氨基]-N-(丁氧羰基)-甲基酯 Chemical Name: 3-[2-[3-(4-Amidinophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-2(S)-(butoxycarboxamido)propionic acid methyl ester monoacetate; 3-[2-[3-(4-Amidinophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-N-(butoxycarbonyl)-L-alanine methyl ester monoacetate
CAS No. 176022-59-6, 170902-47-3 (free base)
项目整合开发状态: Discontinued
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The reaction of N-(butoxycarbonyl)-3-[2-[3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-L-alanine methyl ester (I) (intermediate (VII) in scheme no.22467601a) with hydroxylamine and TEA in hot methanol gives the N-hydroxyamidine compound (II),which is treated with Ac2O in acetic acid to yield the N-acetoxyamidino compound (III).The cyclization of (III) by means of Ac2O in refluxing acetic aid affords the 1,2,4-oxadiazole derivative (IV),which is reduced with H2 over Pd/C in methanol/HOAc to provide the amidino derivative (V).Alternatively,the direct reduction of N-acetoxyamidino derivative (III) with H2 over Pd/C in acetic acid also gives the amidino derivative (V).Finally,the methyl ester group of compound (V) is hydrolyzed with LiOH in THF to yield the target roxifiban acetate.
📌 参考资料/链接：
参考文献标题:An efficient method for the conversion of nitriles to amidines
文献作者:Confalone,P.N.; Li,H.-Y.; Ma,P.(DuPont Pharmaceuticals Co.)
参考来源:WO 9918090
📄 详细内容
合成路线:Reaction of 4-cyanobenzaldehyde (I) with hydroxylamine sulfate in methanol gives 4-cyanobenzaldoxime (II).A 1,3-dipolar cycloaddition of (II) with isobutyl vinylacetate using N-chlorosuccinimide provides the racemic isoxazoline derivative (III).Treatment of (III) with lipase PS30 selectively converts the (R)-isomer to an optically pure acid (IV).Coupling of (IV) with methyl N2-(n-butyloxycarbonyl)-L-2,3-diaminopropionate (VI),which is derived from its corresponding commerically available acid (V),gives the intermediate (VII).Treatment of (VII) with HCl in methanol and ethyl acetate followed by ammonium acetate affords DMP 754 as a crystalline product.Saponification of DMP 754 using LiOH provides the corresponding acid (VIII).
合成路线:The reaction of N-(butoxycarbonyl)-3-[2-[3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-L-alanine methyl ester (I) (intermediate (VII) in scheme no.22467601a) with hydroxylamine and TEA in hot methanol gives the N-hydroxyamidine compound (II),which is treated with Ac2O in acetic acid to yield the N-acetoxyamidino compound (III).The cyclization of (III) by means of Ac2O in refluxing acetic aid affords the 1,2,4-oxadiazole derivative (IV),which is reduced with H2 over Pd/C in methanol/HOAc to provide the amidino derivative (V).Alternatively,the direct reduction of N-acetoxyamidino derivative (III) with H2 over Pd/C in acetic acid also gives the amidino derivative (V).Finally,the methyl ester group of compound (V) is hydrolyzed with LiOH in THF to yield the target roxifiban acetate.
参考文献标题:The chiral specific synthesis of DMP 754,a platelet GPIIb/IIIa antagonist
文献作者:Anzalone,L.; Storace,L.Ward,R.; Kauffman,G.S.; Zhang,L.-H.; Ma,P.
参考来源:Tetrahedron Lett 1996,37(26),4455-8
产品链接: CAS No. 176022-59-6›› 产品链接: CAS No.170902-47-3››