Sodium hydride → HCID 11225598, compound

HRID 2112607Notes

Reaction equation

HRID 2112607 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)[N:5]=[C:4]([NH:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:3]=1[C:19]1[C:24]([F:25])=[CH:23][C:22](F)=[CH:21][C:20]=1[F:27].[CH3:28][N:29]([CH3:34])[CH2:30][CH2:31][CH2:32][OH:33].[H-].[Na+]>CS(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)[N:5]=[C:4]([NH:13][CH2:14][C:15]([F:16])([F:18])[F:17])[C:3]=1[C:19]1[C:20]([F:27])=[CH:21][C:22]([O:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[CH3:28])=[CH:23][C:24]=1[F:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 766463-(Dimethylamino)-1-propanolHCID 11774169HCID 11774169, compound

Product 1

HCID 11225598HCID 11225598, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-chloro-2-(1H-imidazol-1-yl)-N-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine (20 mg, 0.05 mmol) and 3-dimethylamino-1-propanol (103 mg, 1.0 mmol) in 3 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 40 mg, 1.0 mmol). The mixture is stirred at 60° C. for 2 h, cooled to room temperature, and partitioned between ethyl acetate and saturated sodium chloride. The organic layer is washed with saturated sodium chloride (×3), dried over magnesium sulfate, and concentrated. The residue is chromatographed over silica gel, eluting with a gradient of ethyl acetate to 50% methyl alcohol in ethyl acetate. Concentration provides 6-chloro-5-{4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl}-2-(1H-imidazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidin-4-amine as a light tan solid (16 mg, mp 47-49° C.). MS: m/z 491.1 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between ethyl acetate and saturated sodium chloride
  3. washThe organic layer is washed with saturated sodium chloride (×3)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is chromatographed over silica gel
  7. washeluting with a gradient of ethyl acetate to 50% methyl alcohol in ethyl acetate
  8. concentrationConcentration

Sources & evidence

ORD record
ord-e93f16cdad7f4b9c9d58f9e0586c70fa
Source dataset
uspto-grants-2009_04
Patent number
US07524849B2

Reaction notes

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