Tetrahydrofuran → 1-Cyclohexyl-5-[4-(4-hydroxy-1-methyl-4-piperidinyl)-2-methoxyphenyl]-3-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 915948Notes

Reaction equation

HRID 915948 reaction equation
C([Li])CCC.O1CCCC1.Br[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:19][C:20](=[O:34])[C:21]3[N:26]([CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[N:25]=[C:24]([CH3:33])[C:22]=3[N:23]=2)=[C:14]([O:35][CH3:36])[CH:13]=1.[CH3:37][N:38]1[CH2:43][CH2:42][C:41](=[O:44])[CH2:40][CH2:39]1>O>[CH:27]1([N:26]2[C:21]3[C:20](=[O:34])[NH:19][C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:41]5([OH:44])[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]5)=[CH:13][C:14]=4[O:35][CH3:36])=[N:23][C:22]=3[C:24]([CH3:33])=[N:25]2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 740491-Methyl-4-piperidoneHCID 136005882HCID 136005882, compoundHCID 178418339Butyllithium

Product 1

HCID 1360059331-Cyclohexyl-5-[4-(4-hydroxy-1-methyl-4-piperidinyl)-2-methoxyphenyl]-3-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 55.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

In an atmosphere of argon, 0.95 ml of n-butyl lithium (1.59M/hexane solution, 1.51 mmol) was added dropwise at −78° C. to a 10 ml anhydrous tetrahydrofuran solution of 300 mg (0.72 mmol) of the compound obtained in Example 15. The mixture was stirred at −78° C. for 30 minutes, and then 133 μl (1.08 mmol) of 1-methyl-4-piperidone was added, followed by heating the mixture gradually to 0° C. over the course of 1 hour. Then, water was added to the reaction mixture, and then the mixture was 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=100/1) to obtain 179 mg (55%) of the captioned compound.

Workup

  1. temperatureby heating the mixture gradually to 0° C. over the course of 1 hour
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/1)

Sources & evidence

ORD record
ord-0dccdb9d2a3b42118bb24c3baa76b994
Source dataset
uspto-grants-2007_09
Patent number
US07268128B2

Reaction notes

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