新产品编号:1479679

Chemical Name: 3-Benzyl-1-(3-guanidinobenzyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator), Novartis (Originator)
合成路线:N-Boc-Phenylalanine (I) was treated with isobutyl chloroformate and N-methylmorpholine,and the resulting mixed anhydride (II) was coupled to 2-aminobenzophenone (III) to yield the corresponding amide (IV).After Boc deprotection of (IV) with HCl in EtOAc,the intermediate aminoketone was cyclized with NaOH to the benzodiazepine (V).Alkylation of (V) with 3-nitrobenzyl bromide (VI) in the presence of t-BuOK in THF gave the (nitrobenzyl)benzodiazepine (VII).The nitro group of (VV) was subsequently reduced with SnCl2 in boiling EtOAc to affford (VIII).Then,the resulting amine (VIII) was treated with N,N'-di-Boc-thiourea (IX) in the presence of HgCl2 to provide the diprotected guanidine (X),which was finally deprotected with trifluoroacetic acid in CH2Cl2.

合成路线:N-Boc-Phenylalanine (I) was treated with isobutyl chloroformate and N-methylmorpholine,and the resulting mixed anhydride (II) was coupled to 2-aminobenzophenone (III) to yield the corresponding amide (IV).After Boc deprotection of (IV) with HCl in EtOAc,the intermediate aminoketone was cyclized with NaOH to the benzodiazepine (V).This was coupled to p-iodonitrobenzene (VI) in the presence of copper and NaOAc in DMF at 150 C to give the (nitrophenyl)benzodiazepine (VII).The nitro group of (VII) was subsequently reduced with SnCl2 in boiling EtOAc to yield (VIII).Then,the resulting amine (VIII) was treated with N,N'-di-Boc-thiourea (IX) in the presence of HgCl2 to provide the diprotected guanidine (X),which was finally deprotected with trifluoroacetic acid in CH2Cl2.