Cesium carbonate → HCID 11463152, compound

HRID 1831952Notes

Reaction equation

HRID 1831952 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][C:37]([C:38]#[N:39])=[CH:36][CH:35]=2)[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:35]=[CH:36][C:37]([C:38]#[N:39])=[CH:40][CH:41]=2)[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 69060991HCID 69060991, compound

Product 1

HCID 11463152HCID 11463152, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Preparation of 4-[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, the reaction was heated to 80° C., and stirred. Reaction was monitored by LC/MS, and after 4 h was heated to 100° C. and stirred for 16 hours. 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 (40 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J=8.4 Hz, 2H), 7.52 (d, J=8.8 Hz, 2H), 7.44-7.42 (m, 4H), 7.28 (d, J=7.6 Hz, 1H), 7.26 (s, 1H), 6.24 (d, J=7.6 Hz, 1H); 5.31, (s, 2H). ES HRMS m/z 381.0230 (M+H C19H13BrN2O2 requires 381.0233).

Workup

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

Sources & evidence

ORD record
ord-790af1ed25be4d399a58d55111700a97
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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