Water → (RS)-S-[4-({5-bromo-4-[(1R,2R)-2-hydroxy-1-methylpropoxy]pyrimidin-2-yl}amino)phenyl]-S-methyl Sulfoximide

HRID 1891059Notes

Reaction equation

HRID 1891059 reaction equation
[CH3:1][C@@H:2]([OH:6])[C@H:3]([OH:5])[CH3:4].O.[H-].[Na+].[Br:10][C:11]1[C:12](Cl)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[NH:26])=[O:25])=[CH:20][CH:19]=2)=[N:15][CH:16]=1>CS(C)=O>[Br:10][C:11]1[C:12]([O:5][C@H:3]([CH3:4])[C@H:2]([OH:6])[CH3:1])=[N:13][C:14]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[NH:26])=[O:25])=[CH:22][CH:23]=2)=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 225936(2R,3R)-ButanediolHCID 59674032(RS)-S-{4-[(5-bromo-4-chloropyrimidin-2-yl)amino]phenyl}-S-methyl sulfoximide3×

Product 1

HCID 11750351(RS)-S-[4-({5-bromo-4-[(1R,2R)-2-hydroxy-1-methylpropoxy]pyrimidin-2-yl}amino)phenyl]-S-methyl Sulfoximide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent4×

Procedure

A solution of 674 mg (7.5 mmol) of (R,R)-(−)-2,3-butanediol in 6 ml of DMSO is mixed while being cooled with water in portions with 330 mg of sodium hydride (55-60%), and then stirred for 45 minutes at room temperature. The batch is mixed with 196 mg (0.54 mmol) of (RS)—S-{4-[(5-bromo-4-chloropyrimidin-2-yl)amino]phenyl}-S-methyl sulfoximide in 0.5 ml of DMSO and stirred overnight. It is mixed again with 191 mg (0.53 mmol) of (RS)—S-{4-[(5-bromo-4-chloropyrimidin-2-yl)amino]phenyl}-S-methyl sulfoximide in 0.5 ml of DMSO and stirred for another two hours. Finally, it is mixed with 190 mg of (RS)—S-{4-[(5-bromo-4-chloropyrimidin-2-yl)amino]phenyl}-S-methyl sulfoximide (0.53 mmol) in 0.5 ml of DMSO and stirred for one hour. The batch is added to ice water and extracted from ethyl acetate (4×). The combined organic phases are washed with NaCl solution, filtered through a Whatman filter and concentrated by evaporation. The remaining residue is purified by chromatography (DCM/EtOH 9:1). 166 mg (0.41 mmol, corresponding to 25% of theory) of the product is obtained.

Workup

  1. stirringstirred overnight
  2. stirringstirred for another two hours
  3. stirringstirred for one hour
  4. extractionextracted from ethyl acetate (4×)
  5. washThe combined organic phases are washed with NaCl solution
  6. filtrationfiltered through a Whatman
  7. filtrationfilter
  8. concentrationconcentrated by evaporation
  9. customThe remaining residue is purified by chromatography (DCM/EtOH 9:1)
  10. custom166 mg (0.41 mmol, corresponding to 25% of theory) of the product is obtained

Sources & evidence

ORD record
ord-ba8b8efef6794d4d88d0d9374b046a31
Source dataset
uspto-grants-2013_08
Patent number
US08507510B2

Reaction notes

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