Water → HCID 67977685, compound

HRID 1468772Notes

Reaction equation

HRID 1468772 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5]1.Cl[C:18]1[N:19]([CH3:31])[C:20](=[O:30])[CH:21]=[C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][N:25]=2)[N:23]=1.O>CN(C)C=O.C(OCC)(=O)C>[CH3:31][N:19]1[C:20](=[O:30])[CH:21]=[C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][N:25]=2)[N:23]=[C:18]1[O:3][CH:4]1[CH2:9][CH2:8][CH2:7][NH:6][CH2:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5456991-Boc-3-hydroxypiperidineHCID 179544602-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-one

Product 1

HCID 67977685HCID 67977685, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of sodium hydride (60 wt % in mineral oil, 0.24 g, 6.0 mmol) in N,N-dimethylformamide (15 ml) at room temperature under nitrogen atmosphere was added a solution of tert-butyl 3-hydroxypiperidine-1-carboxylate (1.0 g, 5.0 mmol) in N,N-dimethylformamide (5 ml) dropwise. After the mixture was stirred for one hour, 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (1.1 g, 5.0 mmol) was added to the mixture. The resulting mixture was stirred overnight and poured into water. Extractive workup was performed with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. To the residue was added 4N hydrogen chloride in ethyl acetate (10 ml) and the resulting slurry was stirred at room temperature for 2 hours. After concentration under reduced pressure, the residue was dissolved in water. The aqueous solution was washed with ethyl acetate and basified with potassium carbonate. Extraction with chloroform was performed three times and the organic layer was dried over anhydrous sodium sulfate. After concentration, analytically pure 1-methyl-2-(piperidine-3-yloxy)-1H-[4,4′]bipyrimidinyl-6-one was isolated as a white solid (0.66 g, 2.3 mmol, 46%). This compound was used for the next reaction without further purification.

Workup

  1. stirringThe resulting mixture was stirred overnight
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. additionTo the residue was added 4N hydrogen chloride in ethyl acetate (10 ml)
  5. stirringthe resulting slurry was stirred at room temperature for 2 hours
  6. concentrationAfter concentration under reduced pressure
  7. dissolutionthe residue was dissolved in water
  8. washThe aqueous solution was washed with ethyl acetate
  9. extractionExtraction with chloroform
  10. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  11. concentrationAfter concentration

Sources & evidence

ORD record
ord-dc9d43bc1daa417e8b6f54aa0020e17f
Source dataset
uspto-grants-2015_04
Patent number
US09006232B2

Reaction notes

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