Forum

To a solution of 3-(4-(5-(benzyloxy)pyridin-2-yl)-2-methylpiperazin-1-yl)-1-(4-methylbenzy- l)pyrrolidin-2-one (650 mg, 1.381 mmol) in Methanol (20 mL) was added Pd/C (147 mg, 1.381 mmol) at RT. C. was slowly added BBr.sub.3 in DCM (5 mL, 5.00 mmol). To a stirred solution of 6-(piperazin-1-yl)pyridin-3-ol (0.015 g, 0.084 mmol) in DMF (3 mL) was added TEA (0.035 mL, 0.251 mmol) and (S)-1-benzyl-2-oxopyrrolidin-3-ylmethanesulfonate (0.045 g, 0.167 mmol) at RT. To a solution of 6-(piperazin-1-yl)pyridin-3-ol (250 mg, 1.395 mmol) in Acetonitrile (10 mL) was added Triethyl amine (706 mg, 6.97 mmol) and 3-bromo-1-(3-chloro-4-(difluoromethoxy)phenyl)pyrrolidin-2-one (475 mg, 1.395 mmol) at RT. 1-(3-chloro-4-(difluoromethoxy)phenyl)-3-(4-(5-hydroxypyridin-2-yl)p- iperazin-1-yl)pyrrolidin-2-one (100 mg, 0.227 mmol, 16.33% yield). Fractions containing the desired product were combined and dried using a Genevac centrifugal evaporator to get 1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(4-(5-hydroxypyridin-2-yl)piper- azin-1-yl)pyrrolidin-2-one (4.7 mg, 10.25 .mu.mol, 11.05% yield) as pale yellow solid. Fractions containing the desired product were combined and dried using a Genevac centrifugal evaporator to get (60 mg, 0.142 mmol, 4.39% yield) as pale yellow solid. The reaction mixture was cooled to RT and evaporated under reduced pressure to get crude compound which was submitted to SCP.  
  
The residue was purified by SCP. The crude residue was purified by SCP. The crude compound was submitted to SCP. The crude material was purified via preparative LC/MS with the following conditions: Waters Xbridge C18,19.times.150 mm,5 .mu.m; Guard Column:Waters XBridge C18,19.times.10 mm,5 .mu.m; Mobile Phase A:5:95 Acetonitrile:water with 10 mM NH.sub.4OAc; Mobile Phase B: 95:5 Acetonitrile:water with 10 mM NH.sub.4OAc; Gradient:10-45% B over 25 minutes, followed by a 10 minute hold at 45% B and 5 minute hold at 100% B;Flow:15 ml/min. The crude material was purified via preparative LC/MS with the following conditions: Waters Xbridge C18, 19.times.150 mm, 5 .mu.m; Guard Column: Waters XBridge C18,19.times.10 mm,5 .mu.m; Mobile Phase A:5:95 Acetonitrile:water with 10 mM NH.sub.4OAc; Mobile Phase B: 95:5 Acetonitrile:water with 10 mM NH.sub.4OAc; Gradient:5-35% B over 25 minutes, followed by a 10 minute hold at 35% B and 5 minute hold at 100% B; Flow:15 ml/min. The crude material was purified via preparative LC/MS with the following conditions: Waters Xbridge C18,19.times.150 mm,5 .mu.m; Guard Column:Waters XBridge C18,19.times.10 mm,5 .mu.m; Mobile Phase A:5:95 Acetonitrile:water with 10 mM NH4OAc; Mobile Phase B: 95:5 Acetonitrile:water with 10 mM NH4OAc; Gradient:5-35% B over 25 minutes, followed by a 10 minute hold at 35% B and 5 minute hold at 100% B; Flow:15 ml/min.  
  
THF, Flow: 30 ml/min Loadability: 50 mg, T/% B: couple sex cams 0/30,10/60 No.Of Injections: 16, Total Purification Time: 8 min. Chiral purity: Injection Volume: lady gaga sex tape 10, Co-Solvent: 0.3% DEA in Methanol, Column: Chiralcel OD-H(4.6.times.250)mm,5 u, Column Temperature: 23.4, Total Flow: 3, CO2 Flow Rate: 1.8, Co-Solvent Flow Rate: 1.2, Co-Solvent %:40, Back Pressure: 100, RT-2.57 min. Chiral Screening: Injection Volume: 10, Co-Solvent: 0.3% DEA in Methanol, Column: Chiralcel OD-H(4.6.times.250)mm,5 u, Column Temperature: 24.3, my free porn site (visit their website) Total Flow: 3, CO2 Flow Rate: 1.95, Co-Solvent Flow Rate: 1.05, Co-Solvent %: 35, Back Pressure: 101, RT-6.12 min. Chiral Purity: Injection Volume; 10, Co-Solvent: 0.3% DEA in Methanol, Column: Chiralcel OD-H (4.6.times.250) mm,5 u, Column Temperature: 23.5, Total Flow: 3, CO2 Flow Rate: 1.8, Co-Solvent Flow Rate:1.2, Co-Solvent: 40, Back Pressure; 100, RT -5.42 min. Chiral Purity: Injection Volume: 10, Co-Solvent: 0.3% DEA in Methanol, Column: Chiralcel OD-H(4.6.times.250)mm,5 u, Column Temperature: 23.7, Total Flow: 3, CO2 Flow Rate: 1.8, Co-Solvent Flow Rate: 1.2, Co-Solvent %:40, Back Pressure: 99, RT-4.95 min.  
  
Chiral purity: Injection Volume: 10, Co-Solvent: 0.3% DEA in Methanol, Column: Chiralcel OD-H(4.6.times.250)mm,5 u, Column Temperature: 25.9, Total Flow: 3, CO2 Flow Rate: 2.25, Co-Solvent Flow Rate: 0.75, Co-Solvent %: 25, Back Pressure: 100, RT -7.6 min. Chiral screening: Injection Volume: 5, Co-Solvent:0.3% DEA in Methanol, Column: Lux cellulose-4 (4.6.times.250)mm 5 u,Column Temperature: 21.6, CO2 Flow Rate: 2.4, Co-Solvent Flow Rate: 1.6, Co-Solvent %: 40, Total Flow: 4, Back Pressure: 97, RT -4.73 min. 250)mm5 u, Column Temperature: 22.1, CO2 Flow Rate: 2.4, Co-Solvent Flow Rate: 1.6, Co-Solvent:40, Total Flow: 4, Back Pressure: 101, RT -6.6 min. 250)mm5 u, Column Temperature: 22.6, CO2 Flow Rate: 2.4, Co-Solvent Flow Rate: 1.6, Co-Solvent:40, Total Flow: 4, Back Pressure: 97, RT -3.15 min. 4.6)5 u, Column Temperature: 24.6, CO2 Flow Rate: 2.4, Co-Solvent Flow Rate: 1.6, Co-Solvent %: 40, Total Flow: 4, Back Pressure: 103, RT-2.3 min. 5 u, Column Temperature: 25.9, Total Flow: 3, CO2 Flow Rate: 1.8, Co-Solvent Flow Rate: 1.2, Co-Solvent %: 40, Back Pressure: 44, RT-3.05 min. Colvent 100.met; Flow:-total flow 3, CO2 flow rate 2.1, Co-solvent (0.3% DEA in Methanol) 0.9; Column:-Chiralpak AD H (250.times.4.6) mm RT 3.9 min; Purity@ 217 nm:32%, RT 4.7 min; Purity@ 217 nm:16%, RT 6 min; Purity@ 217 nm:16%, RT 10 min; Purity@ 217 nm:33%.