FK-355

Chemical Name: 2-[4-[3,5-Bis(trifluoromethyl)benzoyl]-3(R)-(1H-indol-3-ylmethyl)piperazin-1-yl]-N-(4-methylpiperazin-1-yl)acetamide fumarate
CAS No. 185749-87-5, 185749-84-2 (free base)
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:Coupling of N-Boc-D-formyltryptophan (I) with N-benzylglycine benzyl ester (II) by means of 2-chloro-1-methylpyridinium iodide (CMP) gave the protected dipeptide (III).Acid cleavage of the N-Boc group of (III) ,followed by intramolecular cyclization under basic conditions,produced the diketopiperazine (IV).After basic hydrolysis of the N-formyl group of (IV),the resulting diketopiperazine (V) was reduced to piperazine (VI) using LiAlH4.Subsequent coupling of piperazine (VI) with 3,5-bis(trifluoromethyl)benzoic acid (VII) afforded amide (VIII).The N-benzyl group was then removed by transfer hydrogenolysis with ammonium formate and Pd/C,yielding piperazine (IX).

合成路线:The piperazine (IX) was alkylated with benzyl bromoacetate (X) to give ester (XI),which was converted to carboxylic acid (XII) by catalytic hydrogenolysis of the benzyl ester group.Then,coupling of (XII) with 1-amino-4-methylpiperazine (XIII) produced the corresponding hydrazide.Finally,treatment with fumaric acid in EtOH generated the title fumarate salt.