1-Methylpiperazine → 1-Cyclohexyl-5-[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]-3-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 915922Notes

Reaction equation

HRID 915922 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:28]1[CH:33]=[CH:32][C:31]([C:34]2[NH:35][C:36](=[O:50])[C:37]3[N:42]([CH:43]4[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]4)[N:41]=[C:40]([CH3:49])[C:38]=3[N:39]=2)=[C:30]([O:51][CH3:52])[CH:29]=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:43]1([N:42]2[C:37]3[C:36](=[O:50])[NH:35][C:34]([C:31]4[CH:32]=[CH:33][C:28]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)=[CH:29][C:30]=4[O:51][CH3:52])=[N:39][C:38]=3[C:40]([CH3:49])=[N:41]2)[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 83681Tris(1,1-dimethylethyl)phosphine2×HCID 23676156Sodium t-butoxideHCID 136005882HCID 136005882, compound

Product 1

HCID 1360057831-Cyclohexyl-5-[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]-3-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 38%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

In a stream of argon, 166 μl (1.50 mmol) of N-methylpiperazine, 72 mg (0.75 mmol) of sodium tert-butoxide, 166 mg (0.01 mmol) of tri-tert-butylphosphine, and 1.6 mg (0.008 mmol) of palladium(II) acetate were added to a 2 ml toluene solution of 209 mg (0.50 mmol) of the compound obtained in Example 15, and the mixture was stirred at 110° C. for 2 hours. Further, 166 mg (0.01 mmol) of tri-tert-butylphosphine and 1.6 mg (0.008 mmol) of palladium(II) acetate were added, and the mixture was stirred at 110° C. for 8 hours. Then, the reaction mixture was brought to room temperature, diluted with water, and then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=20/1) to obtain 82 mg (38%) of the captioned compound.

Workup

  1. stirringthe mixture was stirred at 110° C. for 8 hours
  2. customwas brought to room temperature
  3. extractionextracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (chloroform/methanol=20/1)

Sources & evidence

ORD record
ord-2640370e1df244eca668cd5b73958f91
Source dataset
uspto-grants-2007_09
Patent number
US07268128B2

Reaction notes

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