L-054852

Chemical Name: N-[4-(Aminomethyl)-2-pyridinylmethyl]-2(R)-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-ylcarboxamido]-3(S)-methyl-3-(1H-indol-3-yl)propionamide
CAS No. 214471-63-3
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:The intermediate monoprotected diaminopyridine (V) was prepared as shown in Scheme 1.After protection of 4-(aminomethyl)pyridine (I) as the tert-butyl carbamate (II) by means of Boc2O,reaction with peracetic acid yielded the corresponding pyridine N-oxide (III).Subsequent treatment of (III) with trimethylsilyl cyanide and dimethylcarbamyl chloride produced nitrile (IV),which was reduced to the required amine (V) by hydrogenation over Raney-Ni in the presence of ethanolic ammonia.

合成路线:Condensation of beta-methyl-D-tryptophan methyl ester (VI) with disuccinimidyl carbonate (VIII) and then with 4-(2-oxo-1-benzimidazolinyl) piperidine (VII) furnished urea (IX).Basic hydrolysis of the methyl ester of (IX),followed by coupling of the resulting carboxylic acid (X) with the intermediate amine (V) in the presence of EDC and HOBt yielded the corresponding amide (XI).The Boc protecting group of (XI) was finally cleaved with trifluoroacetic acid to give the title compound.