Potassium Phosphate, Tribasic → 4-Methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-amine

HRID 451546Notes

Reaction equation

HRID 451546 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1.[CH3:23][C:24]1([NH2:30])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.Cl[C:32]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34][N:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN1C(=O)CCC1>[CH3:23][C:24]1([NH2:30])[CH2:29][CH2:28][N:27]([C:32]2[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34][N:33]=2)[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, Tribasic2×HCID 5817964-Chloro-6-methylpyrimidineHCID 86656722HCID 86656722, compound

Product 1

HCID 583980494-Methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-amineYield 62%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-methylpiperidin-4-amine bis(4-methylbenzenesulfonate) (3.91 g, 8.53 mmol) and 4-chloro-6-methylpyrimidine (1.10 g, 8.53 mmol) in NMP (35 mL) was added K3PO4 (3.12 g, 17.9 mmol) and the reaction mixture was stirred at 80° C. for 18 hours. After cooling to room temperature, 0.5 M aqueous K3PO4 was added and the mixture extracted twice with dichloromethane. The combined organic layers were extracted twice with HCl (1 N). The combined aqueous layers were made alkaline with NaOH (6 N), extracted twice with dichloromethane and the organic layers washed with brine, dried over sodium sulfate, filtered and evaporated. Purification by chromatography (silica gel, 70 g, 0 to 100% ethyl acetate in heptane; then 0 to 50% methanol in ethyl acetate, containing 10% triethylamine) afforded the title compound (1.09 g, 62%) as a light yellow semisolid.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture extracted twice with dichloromethane
  3. extractionThe combined organic layers were extracted twice with HCl (1 N)
  4. extractionextracted twice with dichloromethane
  5. washthe organic layers washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by chromatography (silica gel, 70 g, 0 to 100% ethyl acetate in heptane
  10. additionthen 0 to 50% methanol in ethyl acetate, containing 10% triethylamine)

Sources & evidence

ORD record
ord-41653e35a10645528c9ee2deca4b3475
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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