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

HRID 219735Notes

Reaction equation

HRID 219735 reaction equation
[H-].[Na+].[C:3]([C:7]1[N:12]=[C:11]([N:13]2[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][OH:22])[CH2:15][CH2:14]2)[CH:10]=[C:9]([CH:23]2[CH2:26][CH2:25][CH2:24]2)[N:8]=1)([CH3:6])([CH3:5])[CH3:4].Cl[C:28]1[CH:33]=[CH:32][N:31]=[C:30]([S:34][CH3:35])[N:29]=1>CCCCC.O1CCOCC1>[C:3]([C:7]1[N:8]=[C:9]([CH:23]2[CH2:26][CH2:25][CH2:24]2)[CH:10]=[C:11]([N:13]2[CH2:14][CH2:15][N:16]([CH2:19][CH2:20][CH2:21][O:22][C:28]3[CH:33]=[CH:32][N:31]=[C:30]([S:34][CH3:35])[N:29]=3)[CH2:17][CH2:18]2)[N:12]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 971134-Chloro-2-methylthiopyrimidineHCID 690262333-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol

Product 1

HCID 690261682-tert-Butyl-4-cyclobutyl-6-{4-[3-(2-methylsulfanyl-pyrimidin-4-yloxy)-propyl]-piperazin-1-yl}-pyrimidineYield 85.2%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

0.36 g of sodium hydride (9 mmol, 60% in paraffin) were washed oil-free with pentane before 1.5 g of 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol (4.5 mmol) dissolved in 20 ml of dioxane were added. The reaction was heated to reflux for 1 h. After cooling, 0.75 g of 4-chloro-2-methylsulfanyl-pyrimidine (4.67 mmol) dissolved in 10 ml of dioxane were added. The reaction mixture was stirred under reflux for 2 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was extracted with 5% aqueous citric acid, the pH of the aqueous phase was adjusted to basic pH with 2 N sodium hydroxide solution. The aqueous layer was re-extracted with ethyl acetate, the organic layer was dried over magnesium sulfate, filtered, and the solvent was evaporated to yield 1.75 g of the title compound as a yellowish oil.

Workup

  1. additionwere added
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 1 h
  4. temperatureAfter cooling
  5. additionwere added
  6. temperatureunder reflux for 2 h
  7. customThe reaction mixture was partitioned between water and ethyl acetate
  8. extractionThe organic layer was extracted with 5% aqueous citric acid
  9. extractionThe aqueous layer was re-extracted with ethyl acetate
  10. dry with materialthe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-5f899c83c1ab494fbe5f4030a4e6e009
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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