Cesium carbonate → HCID 178503226, compound

HRID 724273Notes

Reaction equation

HRID 724273 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]([C:17]2[C:18](Cl)=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)=[O:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][S:27][C:28]1[CH:29]=[C:30]([OH:34])[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]([C:17]2[C:18]([O:34][C:30]3[CH:31]=[CH:32][CH:33]=[C:28]([S:27][CH3:26])[CH:29]=3)=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)=[O:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 99204073-(Methylsulfanyl)phenolHCID 178454040HCID 178454040, compound

Product 1

HCID 178503226HCID 178503226, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

{cis-4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)-amino]-cyclohexyl}-carbamic acid tert-butyl ester (5.44 g, 14.6 mmol), 3-methylsulfanylphenol (2.05 g, 14.6 mmol) and caesium carbonate (7.15 g, 21.9 mmol) were suspended in dimethylformamide (100 ml) and the reaction was heated to 65° C. and stirred at this temperature under nitrogen for 18 h, then at room temperature for 48 h. The reaction was cooled to room temperature, concentrated under reduced pressure and the residue was diluted with water (75 ml). It was then extracted with ethyl acetate (3×100 ml) and the combined organic extracts were washed with water (2×30 ml), brine (30 ml), dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with pentane:ether (50:50 changing to 45:55 then 40:60, by volume) to give (cis-4-{[-5-fluoro-2-(3-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester (3.69 g) as a white solid.

Workup

  1. waitat room temperature for 48 h
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionthe residue was diluted with water (75 ml)
  5. extractionIt was then extracted with ethyl acetate (3×100 ml)
  6. washthe combined organic extracts were washed with water (2×30 ml), brine (30 ml)
  7. dry with materialdried over MgSO4
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel eluting with pentane:ether (50:50 changing to 45:55

Sources & evidence

ORD record
ord-98e8a03dbbe347c7a1582481e20ef37f
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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