Sodium Chloride → HCID 11374666, compound

HRID 1181257Notes

Reaction equation

HRID 1181257 reaction equation
[CH:1]1([C:8]2[N:13]3[CH:14]=[CH:15][N:16]=[C:12]3[N:11]=[C:10](O)[C:9]=2[C:18]2[C:23]([F:24])=[CH:22][C:21](F)=[CH:20][C:19]=2[F:26])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][N:28]([CH3:33])[CH2:29][CH2:30][CH2:31][OH:32].[H-].[Na+].[Cl-:36].[Na+]>CS(C)=O>[Cl:36][C:10]1[C:9]([C:18]2[C:19]([F:26])=[CH:20][C:21]([O:32][CH2:31][CH2:30][CH2:29][N:28]([CH3:33])[CH3:27])=[CH:22][C:23]=2[F:24])=[C:8]([CH:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[N:11]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 766463-(Dimethylamino)-1-propanolHCID 178517377HCID 178517377, compound

Product 1

HCID 11374666HCID 11374666, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of the above 5-cycloheptyl-6-(2,4,6-trifluorophenyl)imidazo[1,2-a]pyrimidin-7-ol and 3-dimethylamino-1-propanol (206 m g, 2.0 mmol) in 3.0 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 80 mg, 2.0 mmol). The mixture is heated at 40° C. for 2 h, and cooled to room temperature. A saturated sodium chloride solution is added, and the product is extracted with ehtyl acetate. The organic solution is washed with saturated sodium chloride (×3), dried over magnesium sulfate, and concentrated. To the residue is added 5 mL of phosphorous oxychloride and 2 mL of N,N-diethylaniline, and the mixture is heated at 110° C. for 1 h. The excess phosphorous oxychloride is removed in vaccuo, and the resulting residue is partitioned between ethyl acetate and 5% sodium carbonate solution. The organic layer is washed with saturated sodium chloride, dried over magnesium sulfate, and concentrated. The residue is chromatographed over silica gel, eluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate. Concentration provides 3-[4-(7-chloro-5-cycloheptylimidazo[1,2-a]pyrimidin-6-yl)-3,5-difluorophenoxy]-N,N-dimethylpropan-1-amine as a brown oil (24 mg). MS: m/z 463.3 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. extractionthe product is extracted with ehtyl acetate
  3. washThe organic solution is washed with saturated sodium chloride (×3)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. additionTo the residue is added 5 mL of phosphorous oxychloride and 2 mL of N,N-diethylaniline
  7. temperaturethe mixture is heated at 110° C. for 1 h
  8. customThe excess phosphorous oxychloride is removed in vaccuo
  9. customthe resulting residue is partitioned between ethyl acetate and 5% sodium carbonate solution
  10. washThe organic layer is washed with saturated sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated
  13. customThe residue is chromatographed over silica gel
  14. washeluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate
  15. concentrationConcentration

Sources & evidence

ORD record
ord-d15cefdbeca74173a4f71856e249e9fa
Source dataset
uspto-grants-2007_10
Patent number
US07285555B2

Reaction notes

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