Sodium Carbonate → HCID 56928761, compound

HRID 1772138Notes

Reaction equation

HRID 1772138 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:20][CH:19]([OH:21])[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C([O:25][CH2:26][C:27]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[CH:29][C:28]=1[N:42]1[CH2:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([C:51]([CH3:54])([CH3:53])[CH3:52])[CH:48]=2)[C:43]1=[O:55])(=O)C.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[C:51]([C:47]1[CH:48]=[C:49]2[C:44](=[CH:45][CH:46]=1)[C:43](=[O:55])[N:42]([C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:20][CH:19]([OH:21])[CH2:18]5)=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=3)[C:27]=1[CH2:26][OH:25])[CH2:50]2)([CH3:54])([CH3:52])[CH3:53]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 580439235-Bromo-3-(5-(3-hydroxyazetidin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-oneHCID 866979362-(5-tert-Butyl-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

Product 1

HCID 56928761HCID 56928761, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was purged with nitrogen and charged with 120c (215 mg, 0.613 mmol), 103f (340 mg, 0.735 mmol), sodium carbonate (195 mg, 1.84 mmol), 1,4-dioxane (8 mL) and water (2 mL). This mixture was degassed with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (71 mg, 0.061 mmol) was added. After heating at 100° C. for 3 h, the reaction mixture was cooled to room temperature and partitioned between water (40 mL) and methylene chloride (100 mL). The layers were separated, and the aqueous phase was extracted with methylene chloride (2×50 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was dissolved in methanol (5 mL), and potassium carbonate (500 mg, 3.62 mmol) was added. After stirring at room temperature for 2 h, the reaction mixture was partitioned between water (20 mL) and methylene chloride (20 mL). The layers were separated, and the aqueous phase was extracted with methylene chloride (2×20 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford 120 in 21% yield (72 mg) as an off-white solid: >250° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.48 (s, 1H), 8.25 (d, 1H, J=2.0 Hz), 7.73-7.71 (m, 2H), 7.62 (d, 1H, J=8.5 Hz), 7.51-7.42 (m, 3H), 7.36 (d, 1H, J=7.5 Hz), 7.28 (d, 1H, J=2.0 Hz), 7.17 (d, 1H, J=9.0 Hz), 6.87 (dd, 1H, J=9.0, 3.0 Hz), 5.56 (d, 1H, J=6.5 Hz), 4.94 (s, 2H), 4.88 (t, 1H, J=5.0 Hz), 4.54 (m, 1H), 4.33 (d, 2H, J=5.0 Hz), 4.02 (t, 2H, J=7.0 Hz), 3.58 (s, 3H), 3.43 (t, 2H, J=7.0 Hz), 1.36 (s, 9H); MS (ESI+) m/z 566.3 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customwas purged with nitrogen
  4. customThis mixture was degassed with nitrogen for 30 min
  5. temperaturethe reaction mixture was cooled to room temperature
  6. custompartitioned between water (40 mL) and methylene chloride (100 mL)
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with methylene chloride (2×50 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe resulting residue was dissolved in methanol (5 mL)
  13. customthe reaction mixture was partitioned between water (20 mL) and methylene chloride (20 mL)
  14. customThe layers were separated
  15. extractionthe aqueous phase was extracted with methylene chloride (2×20 mL)
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-ac026aeeb28244f8a95123886baeb09a
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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