新产品编号:1778677

Chemical Name: 2-[2(S)-Amino-3-(4-hydroxy-2,6-dimethylphenyl)propionyl]-7-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-3(S)-carboxylic acid
项目整合开发状态: Biological Testing
项目研究机构: AstraZeneca (Originator)
合成路线:(S)-7-Hydroxy-1,2,3,4-tetrahydroqinoline-3-carboxylic acid (I) is N-protected by means of di-tert-butyldicarbonate (Boc2O) and Na2CO3 in H2O/dioxane and then converted into methyl ester derivative (II) by treatment with trimethylsilyl diazomethane (TMSCNH2).Reaction of (II) with triflic anhydride (Tf2O) and Et3N in CH2Cl2 yields triflate (III),which is then coupled to boronic acid (IV) by Suzuki cross-coupling reaction in the presence of Pd(PPh3)4 and Na2CO3 in toluene/EtOH,providing derivative (V).Boc removal in (V) by treatment with HCl/HOAc followed by coupling with N-Boc-2,6-dimethyl-D/L-tyrosine (VIa-b) by means of EDC,HOBt,DIEA and DMAP in DMF furnishes protected compound (VIIa-b).Compound (VIIa-b) is hydrolyzed with LiOH and N-deprotected by means of HCl/HOAc to afford a mixture of diastereomers (VIIIa-b) from which the target compound is separated by reverse-phase HPLC.