S-37435
Chemical Name: N-[1(R)-[N-(3-Amino-2-hydroxypropyl)carbamoyl]-2-naphthylethyl]-4-(4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-5-yl)butyramide hydrochloride
CAS No. 220977-91-3, 220979-20-4 ((R)-isomer, free base), 220979-21-5 ((S)-isomer, free base)
项目整合开发状态: Biological Testing
项目研究机构: Kaken (Originator), Molecular Research Institute (Originator)
合成路线:The monoamine intermediate (IV) has been obtained as follows: The condensation of 2(R)-(benzyloxycarbonylamino)-3-(2-naphthyl)propionic acid (I) with 3-(tert-butoxycarbonylamino)-2-hydroxypropylamine (II) gives the corresponding amide (III),which is regioselectively deprotected by hydrogenolysis to yield the desired monoamine (IV).The condensation of 2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one (V) with 4-chlorobutyric acid ethyl ester (VI) gives the corresponding cyclic amide (VII),which is hydrolyzed to afford the carboxylic acid (VIII).The condensation of acid (VIII) with the intermediate amine (IV) provides the amide (IX),which is finally N-deprotected to furnish the target diamide.
📌 参考资料/链接：
参考文献标题:Bicycle amine derivs.
文献作者:Salmon,R.; Sunley,R.L.; Godfrey,C.R.A.; Urch,C.J.; Lewis,T.; Bishop,N.D.(AstraZeneca plc)
参考来源:US 5912254; US 6066646
📄 详细内容
合成路线:The monoamine intermediate (IV) has been obtained as follows: The condensation of 2(R)-(benzyloxycarbonylamino)-3-(2-naphthyl)propionic acid (I) with 3-(tert-butoxycarbonylamino)-2-hydroxypropylamine (II) gives the corresponding amide (III),which is regioselectively deprotected by hydrogenolysis to yield the desired monoamine (IV).The condensation of 2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one (V) with 4-chlorobutyric acid ethyl ester (VI) gives the corresponding cyclic amide (VII),which is hydrolyzed to afford the carboxylic acid (VIII).The condensation of acid (VIII) with the intermediate amine (IV) provides the amide (IX),which is finally N-deprotected to furnish the target diamide.
参考文献标题:Rational design,discovery,and synthesis of a novel series of potent growth hormone secretagogues
文献作者:Huang,P.; Loew,G.H.; Funamizu,H.; Mimura,M.; Ishiyama,N.; Hayashida,M.; Okuno,T.; Shimada,O.; Okuyama,A.; Ikegami,S.; Nakano,J.; Inoguchi,K.
参考来源:J Med Chem 2001,44(24),4082