Talnetant, SB-223412

他奈坦(S)-3-羟基-2-苯基-4-((1-苯基丙基)氨基甲酰基)喹啉-1-鎓氯化物Chemical Name: (-)-3-Hydroxy-2-phenyl-N-[1(S)-phenylpropyl]quinoline-4-carboxamide
CAS No. 174636-32-9, 174636-33-0 ((R)-isomer), 204519-66-4 (monoHCl), 174636-26-1 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Condensation of isatin (I) with 2-methoxyacetophenone (II) in the presence of KOH afforded quinolinecarboxylic acid (III).Subsequent demethylation of the ether function of (III) with refluxing 57% HI gave (IV),which was then condensed with (S)-1-phenylpropyl amine (V) using DCC and HOBt to yield the title amide.

合成路线:The quinolinecarboxylic acid (III) was obtained by the Pfitzinger reaction of isatin (I) with 2-methoxyacetophenone (II) in ethanolic KOH at 80 C.Subsequent methyl ether cleavage in (III) using concentrated HI provided 3-hydroxy-2-phenylquinoline-4-carboxylic acid (IV).Coupling of acid (IV) with (S)-1-phenylpropylamine (V) by means of DCC and HOBt gave amide (VI).Ester (VIII) was then obtained by alkylation of the 3-hydroxy quinoline (VI) with ethyl bromoacetate (VII) in the presence of K2CO3 and KI.Finally,hydrolysis of the ethyl ester (VIII) with refluxing HCl afforded the corresponding carboxylic acid.