Potassium Carbonate → 2-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyrimidin-4-yloxy)-propyl]-piperazin-1-yl}-pyrimidine

HRID 219721Notes

Reaction equation

HRID 219721 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:14]([C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][CH2:32]Cl)[CH2:26][CH2:25]2)[CH:21]=[C:20]([CH:34]2[CH2:37][CH2:36][CH2:35]2)[N:19]=1)([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O>[C:14]([C:18]1[N:19]=[C:20]([CH:34]2[CH2:35][CH2:36][CH2:37]2)[CH:21]=[C:22]([N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][CH2:32][O:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][N:3]=3)[CH2:26][CH2:25]2)[N:23]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 666731042-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidineHCID 178516514HCID 178516514, compound

Product 1

HCID 116687102-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyrimidin-4-yloxy)-propyl]-piperazin-1-yl}-pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

0.2 g of 4-hydroxy-pyrimidine (2.08 mmol) were dissolved in 15 ml of dimethylformamide. After addition of 0.58 g of potassium carbonate (4.16 mmol) and 0.73 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (2.08 mmol), the mixture was stirred at 90° C. for 3 h. The dimethylformamide was removed under reduced pressure and the resulting residue was partitioned between 40 ml of ethyl acetate and 20 ml of water. The aqueous phase was re-extracted with ethyl acetate, the organic layers were combined, dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel with ethyl acetate-methanol (2-10%). Fractions containing the product were combined. The solvent was evaporated. The product crystallized upon standing (yield: 0.2 g).

Workup

  1. customThe dimethylformamide was removed under reduced pressure
  2. customthe resulting residue was partitioned between 40 ml of ethyl acetate and 20 ml of water
  3. extractionThe aqueous phase was re-extracted with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by chromatography on silica gel with ethyl acetate-methanol (2-10%)
  8. additionFractions containing the product
  9. customThe solvent was evaporated
  10. customThe product crystallized

Sources & evidence

ORD record
ord-70bde65aa1254fc1ac25f1928c782f03
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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