4-Fluorophenol → 1,1-Dimethylethyl (2S)-4-({6-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 534791Notes

Reaction equation

HRID 534791 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]2[N:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]3)=[CH:13][CH:12]=2)=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:39][C:40]1[CH:45]=[CH:44][C:43]([OH:46])=[CH:42][CH:41]=1>CN(C=O)C>[F:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][C:2]2[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]3[N:16]=[CH:15][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]4)=[CH:13][CH:12]=3)=[O:9])=[CH:4][CH:3]=2)=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 592622351,1-Dimethylethyl (2S)-4-({6-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate

Product 1

HCID 592622071,1-Dimethylethyl (2S)-4-({6-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylateYield 33.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To 1,1-dimethylethyl (2S)-4-({6-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate (D106) (0.139 g, 0.303 mmol) in DMF (4 mL) under an argon atmosphere was added potassium carbonate (0.293 g, 0.212 mmol) and 4-fluorophenol (0.169 g, 1.51 mmol). The reaction mixture was stirred and heated at 130° C. for 5 h then concentrated in vacuo. The residue was re-dissolved in DCM/water. The organic layer was washed with 2M NaOH solution and brine then dried (Na2SO4) and concentrated to give the crude product which was purified by column chromatography. Elution with EtOAc/DCM gave the title compound as a colourless oil (0.054 g). MS (ES): MH+ 536.2.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in DCM/water
  3. washThe organic layer was washed with 2M NaOH solution and brine
  4. dry with materialthen dried (Na2SO4)
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by column chromatography
  8. washElution with EtOAc/DCM

Sources & evidence

ORD record
ord-2eeed539e4304f3ea7907ff65f0d6843
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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