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| 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 |
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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.
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Received: 28 November 2014
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2015, Vol. 23 
