Dimethylformamide → 2-((S)-1-(8-chloro-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 216881Notes

Reaction equation

HRID 216881 reaction equation
Cl[C:2]1[C:11]([C@@H:12]([N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])[CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([Cl:25])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:26][C:27]([F:34])([F:33])[C:28]1[CH:32]=[CH:31][NH:30][N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>O>[Cl:25][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([N:30]1[CH:31]=[CH:32][C:28]([C:27]([F:34])([F:33])[F:26])=[N:29]1)[C:11]([C@@H:12]([N:14]1[C:15](=[O:24])[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:22]1=[O:23])[CH3:13])=[CH:10]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 18070343-(Trifluoromethyl)pyrazoleHCID 57707774(S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 577079342-((S)-1-(8-chloro-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (0.2000 g, 0.539 mmol), 3-(trifluoromethyl)pyrazole (0.0733 g, 0.539 mmol), cesium carbonate (0.351 g, 1.08 mmol) and in DMF (1.80 mL, 0.539 mmol) was stirred at 100° C. After 2 h, The mixture was cooled to room temperature. To the cooled mixture was added water (30 mL). The mixture was extracted with EtOAc (50 mL×2). The combined organic layers were washed with brine (50 mL×1), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column using 0 to 10% gradient of EtOAc in hexane over 10 min, then 10% isocratic of EtOAc for 10 min, then 10 to 50% gradient of EtOAc in hexane over 20 min, then 50% isocratic of EtOAc for 10 min as eluent to give 2-((S)-1-(8-chloro-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione as a yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (1H, s), 8.51 (1H, d, J=2.2 Hz), 8.25 (1H, dd, J=8.4, 1.0 Hz), 8.08 (1H, dd, J=7.7, 0.9 Hz), 7.63-7.85 (5H, m), 6.92 (1H, d, J=2.7 Hz), 5.94-6.05 (1H, m), 1.83 (3H, d, J=7.0 Hz); LC-MS (ESI) m/z 471.1 [M+H]+.

Workup

  1. extractionThe mixture was extracted with EtOAc (50 mL×2)
  2. washThe combined organic layers were washed with brine (50 mL×1)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column
  7. customover 10 min
  8. wait10% isocratic of EtOAc for 10 min
  9. wait10 to 50% gradient of EtOAc in hexane over 20 min

Sources & evidence

ORD record
ord-5ee3282b1c6e447894e89ac88691f855
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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