Cesium carbonate → HCID 21877234, compound

HRID 724309Notes

Reaction equation

HRID 724309 reaction equation
Cl[C:2]1[N:17]=[CH:16][C:15]([F:18])=[CH:14][C:3]=1[C:4]([NH:6][C:7]1([CH2:12][OH:13])[CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5].[CH3:19][S:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:18][C:15]1[CH:16]=[N:17][C:2]([O:27][C:24]2[CH:25]=[CH:26][C:21]([S:20][CH3:19])=[CH:22][CH:23]=2)=[C:3]([CH:14]=1)[C:4]([NH:6][C:7]1([CH2:12][OH:13])[CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 140864-(Methylthio)phenolHCID 21877189HCID 21877189, compound

Product 1

HCID 21877234HCID 21877234, compoundYield 19.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-Chloro-5-fluoro-N-(1-hydroxymethyl-1-cyclopentyl)-nicotinamide (100 mg, 0.367 mmol), 4-methylsulfanyl phenol (51 mg, 0.367 mmol) and caesium carbonate (131 mg, 0.403 mmol) were suspended in DMF (1.5 ml) and the reaction was heated to 50° C. and stirred at this temperature under nitrogen for 16 h. The reaction mixture was cooled and partitioned between ethyl acetate (25 ml) and water (25 ml). The organic phase was removed and washed with brine (25 ml) followed by water (25 ml). The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 changing to 95:5, by volume) to give 5-Fluoro-N-(1-hydroxymethyl-cyclopentyl)-2-(4-methylsulfanyl-phenoxy)-nicotinamide (27 mg) as an off-white solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate (25 ml) and water (25 ml)
  3. customThe organic phase was removed
  4. washwashed with brine (25 ml)
  5. dry with materialThe organic layer was dried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 changing to 95:5, by volume)

Sources & evidence

ORD record
ord-6282545f7de54d1da193d7d8f18e574a
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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