Triphenylphosphine → HCID 59508997, compound

HRID 1020047Notes

Reaction equation

HRID 1020047 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:27][C:28]1[C:33](B(O)O)=[C:32]([O:37][CH3:38])[CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23]([C:33]3[C:32]([O:37][CH3:38])=[CH:31][CH:30]=[CH:29][C:28]=3[F:27])[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 3294524(2-Fluoro-6-methoxyphenyl)boronic acidHCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 59508997HCID 59508997, compoundYield 5.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To the stirred mixture of 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (0.75 g, 2 mmol) and 6-fluoro-2-methoxy-phenyl boronic acid (0.37 g, 2.2 mmol) in saturated sodium carbonate solution (4 ml) and 1,4-dioxane (4 ml) was added palladium(II) acetate (0.09 g, 0.4 mmol) followed by triphenylphosphine (0.105 g, 0.00 mmol) at room temperature under an atmosphere of nitrogen. The resulting mixture was heated to reflux at 110° C. for one hour and the reaction monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3×100 ml). The organic layers were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA) to afford 4-[6-(2-fluoro-6-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (XXIII) (0.05 g, 4%).

Workup

  1. temperatureThe resulting mixture was heated
  2. filtrationThe reaction mixture was filtered through a celite bed
  3. extractionthe filtrate was extracted with ethyl acetate (3×100 ml)
  4. customThe organic layers were separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA)

Sources & evidence

ORD record
ord-83feb6528f164fc1a45b29db691c4df3
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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