Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
Figure 5
Synthesis of target piperazine derivatives 13a–d and 17.
Reagents and conditions: a) 2-(4-chlorophenyl)acetonitrile, K2CO3, DMSO, reflux, 18 h; b) 4-cyanobenzoyl chloride, Et3N, CH2Cl2, rt, 3 h; c) 4-(chloromethyl)benzonitrile, THF, reflux, 2.5 h; d) NaBH(OAc)3, CH2Cl2, rt, 12 h; e) 4-fluorobenzoyl chloride, Et3N, CH2Cl2, rt, 3 h; f) EDC.HCl, CH2Cl2, rt, 8 h; g) 1-bromo-3-chloropropane, KI, CH3CN, MWI, 15 min; h) 4-fluorobenzoyl chloride, Et3N, CH2Cl2, 0°C, 5 h; i) KI, K2CO3, CH3CN, reflux, 24 h.