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

HRID 219738Notes

Reaction equation

HRID 219738 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:27][C:28]1[N:33]=[CH:32][CH:31]=[CH:30][N:29]=1>CCCCC.O1CCOCC1>[ClH:27].[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[N:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[CH2:17][CH2:18]2)[N:12]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 744042-ChloropyrimidineHCID 690262333-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol

Product 1

HCID 690775862-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-pyrimidine hydrochlorideYield 91.5%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

0.31 g of sodium hydride (7.8 mmol; 60% in paraffin) was washed oil-free with pentane before 1.3 g of 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol (3.91 mmol) dissolved in 20 ml of dioxane were added. The reaction was heated to reflux for 1 h. After cooling, 0.7 g of 2-chloro-pyrimidine (6.11 mmol) dissolved in 10 ml of dioxane were added. The reaction mixture was heated under reflux for 2 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, the solvent evaporated, and the residue re-dissolved in isopropanol and treated with hydrochloric acid in diethyl ether. After removing most of the organic phase, the residue was treated with isopranol/diisopropyl ether, which, after cautious evaporation, yielded 1.6 g of the title compound.

Workup

  1. additionwere added
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 1 h
  4. temperatureAfter cooling
  5. additionwere added
  6. temperatureThe reaction mixture was heated
  7. temperatureunder reflux for 2 h
  8. customThe reaction mixture was partitioned between water and ethyl acetate
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent evaporated
  12. dissolutionthe residue re-dissolved in isopropanol
  13. additiontreated with hydrochloric acid in diethyl ether
  14. customAfter removing most of the organic phase
  15. additionthe residue was treated with isopranol/diisopropyl ether, which
  16. customafter cautious evaporation

Sources & evidence

ORD record
ord-6b01f26efcf8471ab18652023e08c483
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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