Sodium Iodide → HCID 86696742, compound

HRID 2365887Notes

Reaction equation

HRID 2365887 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([N:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[N:20]=3)=[CH:15][C:14]2=[O:32])[CH2:11][OH:12])=[CH:6][C:5]=1[F:33].[I-].[Na+].[CH3:36][S:37][CH2:38]Cl>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([N:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[N:20]=3)=[CH:15][C:14]2=[O:32])[CH2:11][O:12][CH2:36][S:37][CH3:38])=[CH:6][C:5]=1[F:33]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 16916Chloromethyl methyl sulfideHCID 24758Sodium hydrideHCID 71727133HCID 71727133, compound

Product 1

HCID 86696742HCID 86696742, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (44 mg, 1.10 mmol) was added to 1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-(tetrahydropyran-4-ylamino)pyrimidin-4-yl]pyridine-2-one (0.49 g, 1.10 mmol) in DMF (10 mL) at 0° C., which was left to stir at 0° C. In a separate vial, sodium iodide (0.17 g, 1.10 mmol) and chlorodimethyl sulfide (0.11 g, 1.10 mmol) were transferred, which was then added to the reaction mixture. The reaction mixture was stirred overnight at room temperature. The mixture was quenched carefully with water before diluting with ethyl acetate. The phases were separated. The organic phase was washed with saturated sodium bicarbonate, water, and followed by brine. The mixture was dried over sodium sulfate before removing the solvent to leave an oil. The oil was purified by CombiFlash (24 g column, 0-10% MeOH/DCM over 20 minutes) to furnish (S)-1-(1-(4-chloro-3-fluorophenyl)-2-((methylthio)methoxy)ethyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (555 mg) as a solid (M+1=506).

Workup

  1. waitwhich was left
  2. additionwhich was then added to the reaction mixture
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. customThe mixture was quenched carefully with water
  5. additionbefore diluting with ethyl acetate
  6. customThe phases were separated
  7. washThe organic phase was washed with saturated sodium bicarbonate, water
  8. dry with materialThe mixture was dried over sodium sulfate
  9. custombefore removing the solvent
  10. customto leave an oil
  11. customThe oil was purified by CombiFlash (24 g column, 0-10% MeOH/DCM over 20 minutes)

Sources & evidence

ORD record
ord-cbb75feb0de94b9684a9bdf24a27663e
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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