Potassium Carbonate → 1-(3-Bromo-2-pyridinyl)-N-(4-fluorophenyl)-4-piperidinamine

HRID 2424418Notes

Reaction equation

HRID 2424418 reaction equation
Cl[C:2]1[C:7]([Br:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:8][C:7]1[C:2]([N:20]2[CH2:19][CH2:18][CH:17]([NH:16][C:13]3[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=3)[CH2:22][CH2:21]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6933243-Bromo-2-chloropyridineHCID 4778193N-(4-Fluorophenyl)-4-piperidinamine

Product 1

HCID 672469241-(3-Bromo-2-pyridinyl)-N-(4-fluorophenyl)-4-piperidinamineYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloro-3-bromopyridine (0.25 g, 1.3 mmol), D2 (0.25 g, 1.3 mmol) and potassium carbonate (0.23 g, 2.9 mmol) in DMF (5 ml) were heated at 120° C. for 16 h. The mixture was concentrated and the residue partitioned between EtOAc and water (50 ml each). The aqueous was re-extracted with EtOAc (50 ml) and the combined organics washed with water, dried (Na2SO4) and concentrated. Purification by column chromatography on silica (0-50% diethyl ether\40-60 pet. ether gradient) gave the title compound as a yellow solid (0.26 g). δH (CDCl3) 1.64 (2H, m), 2.17 (2H, d), 2.98 (2H, m), 3.43 (2H, m), 3.74 (2H, m), 6.58 (2H, m), 6.77 (1H, m), 6.89 (2H, m), 7.78 (1H, d), 8.22 (1H, dd). MS (ES): MH+ 351.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue partitioned between EtOAc and water (50 ml each)
  3. extractionThe aqueous was re-extracted with EtOAc (50 ml)
  4. washthe combined organics washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by column chromatography on silica (0-50% diethyl ether\40-60 pet. ether gradient)

Sources & evidence

ORD record
ord-c5af9025fd1c48519981f9dfef0663d7
Source dataset
uspto-grants-2011_06
Patent number
US07964602B2

Reaction notes

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