Sodium Bicarbonate → (3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide

HRID 2367417Notes

Reaction equation

HRID 2367417 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4](Cl)[N:3]=1.[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[F:36])#[N:26].C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:30]2[CH:31]=[CH:32][C:27]([C:25]#[N:26])=[C:28]([F:36])[CH:29]=2)[N:3]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 58504476(3S,6R)-1-(2-Amino-6-chloro-4-pyrimidinyl)-6-methyl-N-phenyl-3-piperidinecarboxamide

Product 1

HCID 58504588(3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamideYield 100.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3S,6R)-1-(2-amino-6-chloro-4-pyrimidinyl)-6-methyl-N-phenyl-3-piperidinecarboxamide (8 g, 23.1 mmol) in 1,4-dioxane (250 mL) was added (4-cyano-3-fluorophenyl)boronic acid (5.72 g, 34.7 mmol), Pd(PPh3)4 (2.67 g, 2.3 mmol), and sat. aqueous NaHCO3 (125 mL). The resulting mixture was refluxed overnight, cooled, and diluted with H2O (˜400 mL) to form precipitate. The mixture was filtered, and the gummy solid was dissolved in EtOAc (˜800 mL) and concentrated in vacuo to about 50 mL solvent left. The crude solution was purified by silica gel chromatography (400 g column) eluting with 20% EtOAc/hexanes to 70% EtOAc/hexanes. The fractions that contained the desired product were combined and concentrated in vacuo to afford the title compound (10 g). LC-MS (ES) m/z=431 [M+H]+.

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. temperaturecooled
  3. customto form precipitate
  4. filtrationThe mixture was filtered
  5. dissolutionthe gummy solid was dissolved in EtOAc (˜800 mL)
  6. concentrationconcentrated in vacuo to about 50 mL solvent
  7. waitleft
  8. customThe crude solution was purified by silica gel chromatography (400 g column)
  9. washeluting with 20% EtOAc/hexanes to 70% EtOAc/hexanes
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d826f9bb3d1a47a6af846321c15b4cec
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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