Sodium Carbonate → 4-fluoro-3-(6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)aniline

HRID 527998Notes

Reaction equation

HRID 527998 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH2:12][CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH:16]=3)[N:8](S(C3C=CC=CC=3)(=O)=O)[C:4]=2[N:5]=[CH:6][N:7]=1.[F:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][C:32]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][C:32]=1[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH2:12][CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH:16]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 722211464-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)anilineHCID 904181484-chloro-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 904184944-fluoro-3-(6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)aniline

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of Example 29A (1.10 g, 2.429 mmol), 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (749 mg, 3.16 mmol), and bis(triphenylphosphine)palladium(II) dichloride (170 mg, 0.243 mmol) in 7/2/3 1,2-dimethyoxyethane/ethanol/water (30 mL) was added sodium carbonate (3.64 mL, 7.29 mmol). The mixture was heated at 90° C. for 1 hour, cooled and diluted with 50 mL ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water, and brine, dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 30 mL dioxane, treated with 6M sodium hydroxide (4.05 mL, 24.29 mmol), heated at 100° C. for 1 hour, cooled and diluted with 50 mL ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine, dried over magnesium sulfate, filtered, and concentrated. The residue was triturated with ethyl acetate to give the title compound. MS (ESI+) m/z 388.2 (M+H)+.

Workup

  1. temperaturecooled
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water, and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in 30 mL dioxane
  7. temperatureheated at 100° C. for 1 hour
  8. temperaturecooled
  9. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-bb6b76ef0c834ac38d52094837843ffb
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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