BIM-46068

N-[3-[2(S)-[2(R)-氨基-3-磺基丙基甲基]-3(S)-甲基戊基]-5,5-二甲基-4(R)-噻唑烷基羰基]-L-甲硫氨酸甲基酯Chemical Name: N-[3-[2(S)-[2(R)-Amino-3-sulfanylpropylamino]-3(S)-methylpentyl]-5,5-dimethyl-4(R)-thiazolidinylcarbonyl]-L-methionine methyl ester
CAS No. 201487-53-8
项目整合开发状态: Preclinical
项目研究机构: Biomeasure (Originator)
合成路线:L-5,5-Dimethylthiazolidine-4-carboxylic acid (I) was protected as the N-Boc derivative (II) by treatment with Boc2O and subsequently coupled with L-methionine methyl ester (III) employing EDC and HOBt.The resulting Boc-dipeptide (IV) was then deprotected with trifluoroacetic acid to give (V).On the other hand,Boc-isoleucine (VI) was converted to the N-methoxy amide (VII) by condensation with N,O-dimethylhydroxylamine in the presence of O-benzotriazolyl tetramethyluronium hexafluorophosphate.Reduction of (VII) with LiAlH4 in cold Et2O produced the corresponding aldehyde (VIII).Reductive condensation of thiazolidine (V) with aldehyde (VIII) yielded adduct (IX).The Boc group of (IX) was then deprotected with trifluoroacetic acid to give (X).

合成路线:Protected L-cysteine (XI) was converted to aldehyde (XIII) via formation of the corresponding N-methoxy amide (XII) and further reduction with LiAlH4.Reductive condensation of amine (X) with aldehyde (XIII) in the presence of NaBH4CN furnished (XIV).The Boc group of (XIV) was finally deprotected by treatment with trifluoroacetic acid in the presence of triethylsilane.