Cesium carbonate → HCID 89543690, compound

HRID 922752Notes

Reaction equation

HRID 922752 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH2:14])=[O:13])[CH:3]=1.[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([Cl:23])[C:17]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])O.[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Cu]Cl.CN(C=O)C>[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([Cl:23])[C:17]=1[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH2:14])=[O:13])[CH:3]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 824666HCID 824666, compoundHCID 57497247B-(2,6-Dichloro-4-fluorophenyl)boronic acid

Product 1

HCID 89543690HCID 89543690, compoundYield 9.8%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

4-Bromoquinoline-2-carboxamide (1-8, 50.0 mg, 0.199 mmol, 1.0 equiv.), (2,6-dichloro-4-fluorophenyl)boronic acid (77.0 mg, 0.398 mmol, 2.0 equiv.), cesium carbonate (130.0 mg, 0.398 mmol, 2.0 equiv), Pd(OAc)2 (2.2 mg, 0.01 mmol, 0.05 equiv.), DPPF (11.0 mg, 0.020 mmol, 0.1 equiv.) and copper(I) chloride (19.7 mg, 0.199 mmol, 1.0 equiv.) were added into DMF (1.0 mL). The mixture was stirred at 100° C. overnight. After cooling, aqueous sodium hydrogen carbonate (saturate, 2.0 mL) was added and the mixture was extracted with dichloromethane (2×5 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(2,6-dichloro-4-fluorophenyl)quinoline-2-carboxamide (1-9, 6.20 mg, 9.8%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.281 (s, 1 μl); 8.200-8.226 (m, 1H); 8.175 (br s, 1H); 7.801-7.843 (m, 1H); 7.601-7.637 (m, 2H); 7.137-7.183 (m, 2H); 6.140 (br s, 1H). LRMS m/z (M+H)+ 319.0 found, 319.0 required.

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with dichloromethane (2×5 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-15c6c126321a40c6bf50f452780574f1
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

Loading…