Process Improvement on the Synthesis of Selective BCL-2 Inhibitor——ABT-199
XU Yun-lei, GE Min
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 210009, China
Abstract：4′-Chloro-6-(chloromethyl)-3,3-dimethyl-2,3,4,5-tetrahydro-1,1′-biphenyl（5） was obtained by five-step reaction from 3,3-dimethylcyclohexanone. Tertbutyl 4-｛3-[(1H-pyrrolo［2,3-b］pyridin-5-yl)oxy]-4-(methoxycarbonyl)phenyl｝piperazine-1-carboxylate（10） was prepared by fourstep reaction from 5-bromo-1H-pyrrolo ［2,3-b］ pyridine as the starting material. The selective BCL-2 inhibitor ABT-199 was synthesized by the deprotection of 10， then SN2 displacement with 5， which was followed by the coupling reaction with 3-nitro-4-｛［（tetrahydro-2H-pyran-4-yl)methyl］amino｝benzenesulfonamide. The overall yield was 28.4%. The structure was confirmed by 1H NMRand ESI-MS.
许云雷， 葛敏. BCL-2选择性抑制剂——ABT-199的合成工艺改进[J]. 合成化学, 2015, 23(11): 1063-1067.
XU Yun-lei, GE Min. Process Improvement on the Synthesis of Selective BCL-2 Inhibitor——ABT-199. Chinese Journal of Synthetic Chemistry, 2015, 23(11): 1063-1067.
2015, Vol. 23 
