Sodium hydride → 6-chloro-5-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amine

HRID 2112606Notes

Reaction equation

HRID 2112606 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[N:12][CH:11]=[CH:10][N:9]=2)[N:5]=[C:4]([NH:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])[C:3]=1[C:21]1[C:26]([F:27])=[CH:25][C:24](F)=[CH:23][C:22]=1[F:29].[CH3:30][NH:31][CH2:32][CH2:33][CH2:34][OH:35].[H-].[Na+]>CS(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[N:12][CH:11]=[CH:10][N:9]=2)[N:5]=[C:4]([NH:14][C@@H:15]([CH3:20])[C:16]([F:18])([F:19])[F:17])[C:3]=1[C:21]1[C:26]([F:27])=[CH:25][C:24]([O:35][CH2:34][CH2:33][CH2:32][NH:31][CH3:30])=[CH:23][C:22]=1[F:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 101489863-(Methylamino)-1-propanolHCID 112819276-Chloro-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine

Product 1

HCID 114434706-chloro-5-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amineYield 62.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-chloro-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine (251 mg, 0.58 mmol) and 3-(methylamino)propan-1-ol (267 mg, 3.0 mmol) in 3 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 120 mg, 3.0 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-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amine as a light tan solid (181 mg, mp 48-50° C.). MS: m/z 503.1 (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-a11129f2bed44ff0ab458ac56c35ae06
Source dataset
uspto-grants-2009_04
Patent number
US07524849B2

Reaction notes

Loading…