Cesium carbonate → HCID 11749346, compound

HRID 1866938Notes

Reaction equation

HRID 1866938 reaction equation
BrC1C(=O)NC(C)=CC=1OCC1C=CC(F)=CC=1F.[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][N:31]([C:34]2[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=2[C:36]#[N:37])[C:30](=[O:42])[C:29]=1[Br:43])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC1C=CC(C#N)=CC=1>CS(C)=O>[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][N:31]([C:34]2[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=2[C:36]#[N:37])[C:30](=[O:42])[C:29]=1[Br:43])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 145174-FluorobenzonitrileHCID 69058532HCID 69058532, compound

Product 1

HCID 11749346HCID 11749346, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Preparation of 2-[4-(benzyloxy)-3-bromo-2-oxopyridin-1(2H)-yl]benzonitrile 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (100 mg, 0.36 mmol) was suspended in dimethylsulfoxide (5 mL), cesium carbonate (375 mg, 1.15 mmol) was added and the reaction was shaken for 5 minutes. 4-Fluorobenzonitrile (52 mg, 0.43 mmol) was then added and the reaction was heated to 80° C. with stirring. Reaction was monitored by LC/MS, and after 4 h was heated to 100° C. and stirred for 16 hours. The reaction mixture was partitioned between water and ethyl acetate and extracted with ethyl acetate (5×50 mL). The organic extracts were combined, washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (18 mg, 13%). 1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J=1.2, 8.4 Hz, 1H), 7.73 (dt, J=1.2, 8.0 Hz, 1H), 7.57 (dt, J=0.8, 8.0 Hz, 1H), 7.50-7.36 (m, 6H), 7.27 (d, J=8.0 Hz, 1H), 6.28 (d, J=8.0 Hz, 1H); 5.31 (s, 2H). ES HRMS m/z 381.0249 (M+H C19H13BrN2O2 requires 381.0233).

Workup

  1. stirringwith stirring
  2. customReaction
  3. temperatureafter 4 h was heated to 100° C.
  4. stirringstirred for 16 hours
  5. customThe reaction mixture was partitioned between water and ethyl acetate
  6. extractionextracted with ethyl acetate (5×50 mL)
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated to an oil
  11. custompurified by chromatography (silica gel, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-540f5e5625a741e6a4f8057d69c68360
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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