DNK-333, DNK-333A

Chemical Name: 5-(3,4-Dichlorophenyl)-4(R)-[N-methyl-3,5-bis(trifluoromethyl)benzamido]-N-[2-oxoperhydroazepin-3(R)-yl]-2(E)-pentenamide; N-[1(R)-(3,4-Dichlorobenzyl)-4-[hexahydro-2-oxo-1H-azepin-3(R)-ylamino]-4-oxo-2(E)-butenyl]-N-methyl-3,5-bis(trifluoromethyl)benzamide
CAS No. 203932-02-9
项目整合开发状态: Discontinued
项目研究机构: Novartis (Originator)
合成路线:(3,4-Dichlorophenyl)alanine methyl ester (I) was converted to the N-Boc amino ester (II),which was subsequently alkylated with iodomethane in the presence of Ag2O,yielding the N-methyl derivative (III).Partial reduction of the ester group of (III) to the aldehyde (IV) was carried out using DIBAL in toluene at -78 C.Horner-Emmons reaction of aldehyde (IV) with triethyl phosphonoacetate (V) furnished the arylpentenoate ester (VI),which was further hydrolyzed to acid (VII) with LiOH.Coupling of acid (VII) with D-3-amino-epsilon-caprolactam (VIII) gave rise to amide (IX).The N-Boc group of (IX) was removed by treatment with trifluoroacetic acid,and the resulting amine (X) was finally acylated with 3,5-bis(trifluoromethyl)benzoyl chloride to produce the target amide.