Potassium Carbonate → (1-(3-Bromo-5-fluoropyridin-4-yl)piperidin-4-yl)(4-methylpiperazin-1-yl)methanone

HRID 524884Notes

Reaction equation

HRID 524884 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1.Cl.[Br:19][C:20]1[CH:21]=[N:22][CH:23]=[C:24]([F:27])[C:25]=1Cl.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[Br:19][C:20]1[CH:21]=[N:22][CH:23]=[C:24]([F:27])[C:25]=1[N:15]1[CH2:16][CH2:17][CH:12]([C:10]([N:7]2[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]2)=[O:11])[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 45036889(4-Methylpiperazin-1-yl)piperidin-4-yl-methanone dihydrochlorideHCID 867209403-Bromo-4-chloro-5-fluoropyridine hydrochloride

Product 1

HCID 86720941(1-(3-Bromo-5-fluoropyridin-4-yl)piperidin-4-yl)(4-methylpiperazin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (4-methylpiperazin-1-yl)-(4-piperidyl)methanone dihydrochloride (50.65 g, 178.2 mmol), 3-bromo-4-chloro-5-fluoro-pyridine hydrochloride 18 (40 g, 162 mmol) and dipotassium carbonate (94.04 g, 680.4 mmol) in NMP (400 mL) was heated at 150° C. overnight. The mixture was cooled to room temperature then filtered to remove inorganic salts and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc (800 mL), washed with brine (100 mL×4), dried (MgSO4), filtered and concentrated in vacuo to afford a brown viscous oil. This residue was purified by silica gel column (approx 800 g of silica), product loaded onto silica in DCM, then eluting with 3% methanol (containing 10% ammonium hydroxide)/DCM to afford the desired product as a brown oil which crystallised on standing (27.44 g, 44%). MS (ES+) 387.1.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationthen filtered
  3. customto remove inorganic salts
  4. concentrationthe filtrate was concentrated in vacuo
  5. dissolutionThe residue was dissolved in EtOAc (800 mL)
  6. washwashed with brine (100 mL×4)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford a brown viscous oil
  11. customThis residue was purified by silica gel column (approx 800 g of silica), product
  12. washeluting with 3% methanol (containing 10% ammonium hydroxide)/DCM

Sources & evidence

ORD record
ord-3503f955754c47969e6c37228d79434e
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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