4-{4-[3-(4-Benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclobutyl-pyrimidine → 2-{3-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propoxy}-pyrimidin-4-ol

HRID 219737Notes

Reaction equation

HRID 219737 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([O:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][N:22]([C:25]3[CH:30]=[C:29]([CH:31]4[CH2:34][CH2:33][CH2:32]4)[N:28]=[C:27]([C:35]([CH3:38])([CH3:37])[CH3:36])[N:26]=3)[CH2:21][CH2:20]2)[N:10]=1)C1C=CC=CC=1>O1CCCC1.[Pd]>[C:35]([C:27]1[N:26]=[C:25]([N:22]2[CH2:21][CH2:20][N:19]([CH2:18][CH2:17][CH2:16][O:15][C:11]3[N:10]=[C:9]([OH:8])[CH:14]=[CH:13][N:12]=3)[CH2:24][CH2:23]2)[CH:30]=[C:29]([CH:31]2[CH2:32][CH2:33][CH2:34]2)[N:28]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

4

Reactant 1

HCID 690276004-{4-[3-(4-Benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclobutyl-pyrimidine

Product 1

HCID 1784415752-{3-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propoxy}-pyrimidin-4-olYield 59.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

0.75 g of 4-{4-[3-(4-benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclobutyl-pyrimidine (1.45 mmol) were dissolved in 20 ml of tetrahydrofuran and, after addition of 0.1 g of 10% Pd/C, the reaction mixture was hydrogenated for 3 h at 40° C. After filtration, additional catalyst (0.2 g of 10% Pd/C) was added and the mixture was again hydrogenated for 1 h at 40° C. Finally, the catalyst was removed by filtration, the solvent evaporated under reduced pressure, and the remaining oil crystallized by addition of acetonitril to yield 0.37 g of the title compound.

Workup

  1. filtrationAfter filtration, additional catalyst (0.2 g of 10% Pd/C)
  2. additionwas added
  3. waitthe mixture was again hydrogenated for 1 h at 40° C
  4. customFinally, the catalyst was removed by filtration
  5. customthe solvent evaporated under reduced pressure
  6. customthe remaining oil crystallized by addition of acetonitril

Sources & evidence

ORD record
ord-da44e480985d411bb6042fa662a41b9c
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

Loading…