4-Phenylpiperidine → 2-Methyl-6-methylamino-4-(4-phenylpiperidino)pyrimidine

HRID 1655849Notes

Reaction equation

HRID 1655849 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=1.[C:11]1([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:10][C:4]1[N:3]=[C:2]([N:20]2[CH2:19][CH2:18][CH:17]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:22][CH2:21]2)[CH:7]=[C:6]([NH:8][CH3:9])[N:5]=1

Participants

3

Reactant 2

HCID 698734-PhenylpiperidineHCID 197895186-chloro-N,2-dimethylpyrimidin-4-amine

Product 1

HCID 197895132-Methyl-6-methylamino-4-(4-phenylpiperidino)pyrimidineYield 75%

Procedure

A mixture of 4-chloro-2-methyl-6-methylaminopyrimidine (525 mg, 3.3 mM; described in J. Pharm. Soc. (Japan) 1966, 86, p. 952) and 4-phenylpiperidine (1.08 g, 6.6 mM) was heated as a melt at 135°-140° C. for 1 hour. The residue, obtained after cooling, was triturated with ether and the mixture separated by filtration. The solid was suspended in a mixture of 50% w/v potassium hydroxide solution (50 ml) and isopropanol (50 ml). The mixture was heated under reflux for 2 hours and cooled. The organic layer was separated and the solvent removed in vacuo. The residue was dissolved in methylene chloride (50 ml), washed with water (2×25 ml), dried (MgSO4) and the solvent evaporated. The residue was purified by flash chromatography on silica (Merck Art. 9385, 100 g), using a mixture of methanol and methylene chloride (1:9 v/v) as eluant, to give 2-methyl-6-methylamino-4-(4-phenylpiperidino)-pyrimidine (700 mg, 75% yield), m.p. 186°-188° C.; microanalysis, found: C, 71.6; H,7.5; N,19.3%; C17H22N4.1/4H2O requires C,71.2; H,7.8; N,19.5%.

Workup

  1. temperaturewas heated as a melt at 135°-140° C. for 1 hour
  2. customThe residue, obtained
  3. temperatureafter cooling
  4. customwas triturated with ether
  5. customthe mixture separated by filtration
  6. additionThe solid was suspended in a mixture of 50%
  7. temperatureThe mixture was heated
  8. temperatureunder reflux for 2 hours
  9. temperaturecooled
  10. customThe organic layer was separated
  11. customthe solvent removed in vacuo
  12. dissolutionThe residue was dissolved in methylene chloride (50 ml)
  13. washwashed with water (2×25 ml)
  14. dry with materialdried (MgSO4)
  15. customthe solvent evaporated
  16. customThe residue was purified by flash chromatography on silica (Merck Art. 9385, 100 g)
  17. additiona mixture of methanol and methylene chloride (1:9 v/v) as eluant

Sources & evidence

ORD record
ord-cb16b10ff98741fea498c5887df0b303
Source dataset
uspto-grants-1993_10
Patent number
US05252567

Reaction notes

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