Water → 5-chloro-6-{4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine

HRID 1786292Notes

Reaction equation

HRID 1786292 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:13]([F:14])=[CH:12][C:11](F)=[CH:10][C:9]=2[F:16])=[C:6]([NH:17][C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])[N:5]2[N:24]=[CH:25][N:26]=[C:4]2[N:3]=1.[CH3:27][N:28]([CH3:33])[CH2:29][CH2:30][CH2:31][OH:32].[H-].[Na+].O>CS(C)=O>[Cl:1][C:2]1[C:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([O:32][CH2:31][CH2:30][CH2:29][N:28]([CH3:33])[CH3:27])=[CH:10][C:9]=2[F:16])=[C:6]([NH:17][C@@H:18]([CH3:23])[C:19]([F:22])([F:20])[F:21])[N:5]2[N:24]=[CH:25][N:26]=[C:4]2[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 766463-(Dimethylamino)-1-propanolHCID 119750435-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 113992225-chloro-6-{4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amineYield 67.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine (600 mg, 1.5 mmol) and 3-dimethylamino-1-propanol (1.03 g, 10 mmol) in 5 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 400 mg, 10 mmol). The mixture is heated at 50° C. for 30 min, and cooled to room temperature. Water is added to quench the reaction, and the product is extracted with ethyl acetate (x2). The combined organic extracts are washed with saturated sodium chloride (x4), dried over magnesium sulfate, and concentrated to a residue. The residue is chromatographed over silica gel, eluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate. Concentration provides 5-chloro-6-{4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine as a colorless oil (486 mg). MS: m/z 479.2 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. customto quench
  3. customthe reaction
  4. extractionthe product is extracted with ethyl acetate (x2)
  5. washThe combined organic extracts are washed with saturated sodium chloride (x4)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated to a residue
  8. customThe residue is chromatographed over silica gel
  9. washeluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate
  10. concentrationConcentration

Sources & evidence

ORD record
ord-421dbdeda10342f28090350c0dc828e7
Source dataset
uspto-grants-2009_03
Patent number
US07507739B2

Reaction notes

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