PD-180849

Chemical Name: N-[1(S)-[1-Amidino-3-piperidinylmethyl]-2-oxo-2-(2-thiazolyl)ethyl]-2-[2(R)-(2-chlorobenzyl)-3,6-dioxo-4-(3-phenylpropyl)piperazinyl]acetamide
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator), Shire BioChem (Originator)
合成路线:Alkylation of 3-phenylpropylamine (I) with methyl bromoacetate (II) provided secondary amine (III),which was coupled with N-Boc-(2-chlorophenyl)alanine (IV) using diisopropyl carbodiimide (DIC) and 7-hydroxy azabenzotriazole (HOAt).After deprotection of the Boc group from the resulting amide (V) with trifluoroacetic acid,cyclization in the presence of Et3N in refluxing MeOH funished piperazinedione (VI).The amide N of (VI) was alkylated with tert-butyl bromoacetate,and the tert-butyl group was then removed using trifluoroacetic acid to provide piperazineacetic acid (VII).This was then coupled to protected amino acid (VIII) by means of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and HOAt to give (IX).Finally,the 2,2,5,7,8-pentamethylchroman-6-sulfonyl protecting group of (IX) was removed with trifluoroacetic acid to furnish the target compound.