Water → (3S,6R)-1-(2-Amino-6-chloro-4-pyrimidinyl)-6-methyl-N-phenyl-3-piperidinecarboxamide

HRID 2367416Notes

Reaction equation

HRID 2367416 reaction equation
[CH3:1][C@H:2]1[NH:7][CH2:6][C@@H:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[CH2:4][CH2:3]1.[Cl:17][C:18]1[CH:23]=[C:22](Cl)[N:21]=[C:20]([NH2:25])[N:19]=1.C([O-])(O)=O.[Na+].O>O1CCOCC1.CCOC(C)=O.ClC1C=C(Cl)N=C(N)N=1>[NH2:25][C:20]1[N:21]=[C:22]([N:7]2[C@H:2]([CH3:1])[CH2:3][CH2:4][C@H:5]([C:8]([NH:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:9])[CH2:6]2)[CH:23]=[C:18]([Cl:17])[N:19]=1

Participants

8

Reactant 4

HCID 962WaterHCID 655222-Amino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 44174107(3S,6R)-6-Methyl-N-phenyl-3-piperidinecarboxamide

Product 1

HCID 58504476(3S,6R)-1-(2-Amino-6-chloro-4-pyrimidinyl)-6-methyl-N-phenyl-3-piperidinecarboxamideYield 116.8%

Reagents, catalysts & solvents 3

HCID 655222-Amino-4,6-dichloropyrimidineCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3S,6R)-6-methyl-N-phenyl-3-piperidinecarboxamide (12 g, 55 mmol) in 1,4-dioxane (250 mL) was added 4,6-dichloro-2-pyrimidinamine (8.11 g, 49.5 mmol) and sat. aqueous NaHCO3 (125 mL), and the reaction mixture was then refluxed overnight. The reaction was not completed. The reaction mixture was cooled, added 4,6-dichloro-2-pyrimidinamine (0.9 g, 5.5 mmol), and refluxed overnight. When the reaction was completed, the mixture was cooled down. To the mixture was added about 500 mL of H2O to form a precipitate, and then filtered to obtain a gummy solid. The gummy solid was then dissolved in EtOAc (˜800 mL). The organic solution was washed with water (2×200 mL), brine (200 mL), dried (Na2SO4), filtered, and concentrated in vacuo to afford the crude title compound (20 g). LC-MS (ES) m/z=346 [M+H]+.

Workup

  1. temperaturethe reaction mixture was then refluxed overnight
  2. temperatureThe reaction mixture was cooled
  3. temperaturerefluxed overnight
  4. temperaturethe mixture was cooled down
  5. customto form a precipitate
  6. filtrationfiltered
  7. customto obtain a gummy solid
  8. washThe organic solution was washed with water (2×200 mL), brine (200 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7200e9f940fe45cf9c640dce67bd19cf
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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