新产品编号:419739
Chemical Name: Nalpha-[trans-4-Ethoxy-1-(sulfanylmethyl)-1-cyclohexylcarbonyl]-N1-(3-pyridyl)-L-phenylalaninamide
CAS No. 213915-01-6
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II).Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1).Then,alkylation of (III) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV),which was hydrolyzed with ethanolic KOH to the carboxylic acid (V).Coupling of N-Boc-L-phenylalanine (VI) with benzylamine in the presence of EDC and HOBt produced amide (VII),and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-benzylamide (VIII).This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX),which was debenzylated by catalytic hydrogenation yielding alcohol (X).
合成路线:The mesylation of alcohol (X) yielded mesylate (XI),which was treated with potassium thioacetate to afford the thioacetate ester (XII).Finally,this thioacetate was hydrolyzed to the target thiol with NaOH.
合成路线:Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II).Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1).Then,alkylation of (II) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV),which was hydrolyzed with ethanolic KOH to the carboxylic acid (V).Coupling of N-Boc-L-phenylalanine (VI) with 3-pyridylamine in the presence of EDC and HOBt produced amide (VII),and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-(3-pyridyl)amide (VIII).This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX),which was debenzylated by catalytic hydrogenation yielding alcohol (X).
合成路线:The mesylation of alcohol (X) yielded mesylate (XI),which was treated with potassium thioacetate to afford the thioacetate ester (XII).Finally,this thioacetate was hydrolyzed to the target thiol with NaOH.
📌 参考资料/链接：
参考文献标题:Certain cyclic thio substd.acylaminoacid amide derivs.
文献作者:Fink,C.A.(Novartis AG)
参考来源:EP 0966439; US 6034136; WO 9842662
📄 详细内容
合成路线:Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II).Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1).Then,alkylation of (III) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV),which was hydrolyzed with ethanolic KOH to the carboxylic acid (V).Coupling of N-Boc-L-phenylalanine (VI) with benzylamine in the presence of EDC and HOBt produced amide (VII),and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-benzylamide (VIII).This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX),which was debenzylated by catalytic hydrogenation yielding alcohol (X).
合成路线:The mesylation of alcohol (X) yielded mesylate (XI),which was treated with potassium thioacetate to afford the thioacetate ester (XII).Finally,this thioacetate was hydrolyzed to the target thiol with NaOH.
合成路线:Ethyl 4-hydroxybenzoate (I) was alkylated with EtI and K2CO3 to afford ethyl ether (II).Subsequent hydrogenation of (II) over Rh/C produced ethyl 4-ethoxycyclohexane carboxylate (III) (1).Then,alkylation of (II) using benzyl chloromethyl ether and LDA gave the benzyloxymethyl compound (IV),which was hydrolyzed with ethanolic KOH to the carboxylic acid (V).Coupling of N-Boc-L-phenylalanine (VI) with 3-pyridylamine in the presence of EDC and HOBt produced amide (VII),and further acid deprotection of the Boc group of (VII) yielded phenylalanine-N-(3-pyridyl)amide (VIII).This was coupled with carboxylic acid (V) by means of DCC and HOAt to provide diamide (IX),which was debenzylated by catalytic hydrogenation yielding alcohol (X).
合成路线:The mesylation of alcohol (X) yielded mesylate (XI),which was treated with potassium thioacetate to afford the thioacetate ester (XII).Finally,this thioacetate was hydrolyzed to the target thiol with NaOH.
参考文献标题:Design and synthesis of thiol containing inhibitors of matrix metalloproteinases
文献作者:Fink,C.A.; Carlson,J.E.; Boehm,C.; McTaggart,P.; Qiao,Y.; Doughty,J.; Ganu,V.; Melton,R.; Goldberg,R.
参考来源:Bioorg Med Chem Lett 1999,9(2),195