Cesium carbonate → HCID 178428842, compound

HRID 1465536Notes

Reaction equation

HRID 1465536 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[N:10]=[C:11]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:12][CH:13]=2)=[C:4]([CH3:23])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:31]1[CH:32]=[CH:33][C:34]([O:37]C)=[N:35][CH:36]=1>CN(C=O)C>[OH:37][C:34]1[N:35]=[CH:36][C:31]([O:1][C:2]2[CH:3]=[C:4]([CH3:23])[C:5]([C:9]3[N:10]=[C:11]([NH:14][C:15](=[O:22])[C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[S:12][CH:13]=3)=[C:6]([CH3:8])[CH:7]=2)=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27348955-Bromo-2-methoxypyridineHCID 86690827HCID 86690827, compound

Product 1

HCID 178428842HCID 178428842, compoundYield 39.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of N-(4-(4-hydroxy-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (5-3, 1.92 g, 5.91 mmol) in DMF (15 mL) were added cesium carbonate (2.41 g, 7.39 mmol) and Cu (116 mg, 1.78 mmol, 0.30 equiv). The mixture was stirred at 80-90° C. for 60 min. 5-Bromo-2-methoxy-pyridine (9-1, 1.67 g, 8.87 mmol) was added to the solution and the reaction mixture was stirred at 100° C. for additional 24 hr. The solution was quenched with water (40 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3) to give 5 (0.97 g) in 38% yield: 1H NMR (CDCl3, 500 MHz) δ 8.89 (d, J=5.0 Hz, 2H), 8.23 (d, J=5.0 Hz, 2 H), 8.02 (s, 1 H), 7.37 (d, J=3.0 Hz, 1 H), 6.89 (s, 1 H), 6.80 (d, J=9.0 Hz, 1 H), 6.69 (s, 2 H), 3.94 (s, 3H), 2.17 (s, 6 H), ESI-MS=m/z 433.2 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at 100° C. for additional 24 hr
  2. customThe solution was quenched with water (40 mL)
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3)

Sources & evidence

ORD record
ord-9e327d3d11194a8cb9ac7f68703e44da
Source dataset
uspto-grants-2015_04
Patent number
US08999983B2

Reaction notes

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