Cesium carbonate → Methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate

HRID 922807Notes

Reaction equation

HRID 922807 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:8][C:9]1[C:18]([F:19])=[C:17]2[C:12]([C:13]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)=[CH:14][C:15]([C:20]([O:22][CH3:23])=[O:21])=[N:16]2)=[CH:11][CH:10]=1.FC(F)(F)C1OCCNC1>CN(C=O)C.CCOC(C)=O>[F:19][C:18]1[C:9]([CH3:8])=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=[C:13]2[C:24]1[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 535348452-(Trifluoromethyl)morpholineHCID 89545201methyl 7-(bromomethyl)-8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate

Product 1

HCID 89545232Methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cs2CO3 (345 mg, 1.06 mmol) was added to a mixture of methyl 7-(bromomethyl)-8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate (7-18, 160 mg, 0.42 mmol) and 2-(trifluoromethyl)morpholine (79 mg, 0.51 mmol) in DMF (4.2 mL). After stirring at room temperature for 2 h, the mixture was diluted with EtOAc, washed with H2O, then brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexane (0-100%) to afford methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate as racemic mixture (31.4 mg, 16%). LRMS m/z (M+H)+ 453.3 found, 453.1 required. Chiral separation using SFC chromatography provided (R)-methyl 8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-7-((2-(trifluoromethyl)morpholino)methyl)quinoline-2-carboxylate (7-19a, 15 mg) and (S)-methyl 8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-7-((2-(trifluoromethyl)morpholino)methyl)quinoline-2-carboxylate (7-19b, 14.3 mg).

Workup

  1. washwashed with H2O
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with EtOAc/Hexane (0-100%)

Sources & evidence

ORD record
ord-dab13dc3acb44e618279715aa658486c
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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