Sodium hydride → HCID 178503206, compound

HRID 724337Notes

Reaction equation

HRID 724337 reaction equation
Cl[CH:2]([CH3:33])[CH2:3][CH2:4][C:5]([NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=[O:32])[C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[N:18][C:17]=2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([S:30][CH3:31])[CH:25]=2)[CH2:10][CH2:9]1)=[O:6].[H-].[Na+]>CN1CCCC1>[F:22][C:20]1[CH:19]=[N:18][C:17]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([S:30][CH3:31])[CH:25]=2)=[C:16]([CH:21]=1)[C:15]([NH:14][C@H:11]1[CH2:12][CH2:13][C@@H:8]([N:7]2[CH2:33][CH2:2][CH2:3][CH2:4][C:5]2=[O:6])[CH2:9][CH2:10]1)=[O:32]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 178503221HCID 178503221, compound

Product 1

HCID 178503206HCID 178503206, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Procedure

cis-N-[4-(4-Chloro-pentoylamino)-cyclohexyl]-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide (259 mg, 0.486 mmol) was dissolved in N-methylpyrrolidine (5 ml) under nitrogen at room temperature and sodium hydride (60% dispersion in mineral oil, 49 mg, 1.21 mmol) was added. The reaction was stirred at room temperature for 18 h and quenched with water (10 ml) then extracted with ethyl acetate (5×10 ml). The combined organic extracts were washed with water (3×5 ml), brine (5 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (97:3, by volume) and the product was triturated with diethylether (2 ml) to give 5-Fluoro-2-(3-methylsulfanyl-phenoxy)-N-[cis-4-(2-oxo-piperidin-1-yl)-cyclohexyl]-nicotinamide (69 mg) as a white solid.

Workup

  1. customquenched with water (10 ml)
  2. extractionthen extracted with ethyl acetate (5×10 ml)
  3. washThe combined organic extracts were washed with water (3×5 ml), brine (5 ml)
  4. dry with materialdried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (97:3, by volume)
  7. customthe product was triturated with diethylether (2 ml)

Sources & evidence

ORD record
ord-00005c17b7a24960b7058e8bffb24e36
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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