VX-148

Chemical Name: N-[1(S)-[3-[3-(4-Cyano-3-methoxyphenyl)ureido]phenyl]ethyl]carbamic acid 1(R)-(cyanomethyl)propyl ester
CAS No. 297730-04-2
项目整合开发状态: Phase II
项目研究机构: Vertex (Originator)
合成路线:The intermediate carbamate (V) has been obtained as follows.The reaction of 4-bromo-3-methoxynitrobenzene (I) with CuCN in NMP at 150 C gives 2-methoxy-4-nitrobenzonitrile (II),which is reduced with H2 over Pd/C in ethyl acetate to yield 4-amino-2-methoxybenzonitrile (III).Finally,this compound is condensed with phenyl carbamate (IV) by means of NaHCO3 in ethyl acetate to afford the desired carbamate intermediate (V).

合成路线:The reduction of 3-nitroacetophenone (VI) by means of NaBH4 in ethanol gives 1-(3-nitrophenyl)ethanol (VII),which is treated with DPPA and DBU in hot toluene to yield the azido derivative (VIII).The reduction of (VIII) with PPh3 in THF/water affords 1-(3-nitrophenyl)ethylamine (IX) as a racemic mixture that is submitted to optical resolution with L-(+)-tartaric acid to provide the desired (S)-isomer (X).The reduction of the nitro group of (X) by means of H2 over Pd/C in methanol gives 1(S)-(3-aminophenyl)ethylamine (XI),which is condensed with 2(R)-hydroxypentanenitrile (XII) and CDI to yield the carbamate (XIII).Finally,this compound is condensed with intermediate carbamate (V) by means of TEA in hot ethyl acetate to afford the target urea.