Potassium Carbonate → HCID 66760648, compound

HRID 389431Notes

Reaction equation

HRID 389431 reaction equation
Cl[C:2]1[O:11][C:5]2=[C:6]([NH2:10])[N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1.[CH:12]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[C:16]=2[CH:15]=[CH:14][N:13]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[CH:12]1[C:21]2[C:16](=[C:17]([C:2]3[O:11][C:5]4=[C:6]([NH2:10])[N:7]=[CH:8][CH:9]=[C:4]4[CH:3]=3)[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 599474Isoquinoline-5-boronic acidHCID 66759887HCID 66759887, compound

Product 1

HCID 66760648HCID 66760648, compoundYield 90.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-chlorofuro[2,3-c]pyridin-7-amine (4.0 g, 23.8 mmol) and 5-isoquinoline boronic acid (4.33 g, 25.0 mmol) in 1,4-dioxane (150 mL) and water (50 mL) was sparged with nitrogen for 15 min and then treated with Pd(PPh3)2Cl2 (250 mg). After sparging with nitrogen for another 5 min, K2CO3 (2.2 g, 59.5 mmol) was added and the mixture heated at reflux overnight. The 1,4-dioxane was removed in vacuo and DCM was added. The phases were separated and the organic phase was washed with water, then brine. The solution was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (2% MeOH:DCM) to provide the 5.6 g (90%) of the title compound. 1H NMR (300 MHz, CD3OD): δ 6.99 (d, J=5.4 Hz, 1H), 7.27 (s, 1H), 7.73 (d, J=5.4 Hz, 1H); 7.81 (t, J=8.1 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.29 (dd, J=7.4 Hz, J=1.0 Hz, 1H), 8.44 (d, J=5.4 Hz, 1H), 8.55 (d, J=6.0 Hz, 1H); 9.32 (s, 1 H).

Workup

  1. customwas sparged with nitrogen for 15 min
  2. additiontreated with Pd(PPh3)2Cl2 (250 mg)
  3. customAfter sparging with nitrogen for another 5 min
  4. temperaturethe mixture heated
  5. temperatureat reflux overnight
  6. customThe 1,4-dioxane was removed in vacuo and DCM
  7. additionwas added
  8. customThe phases were separated
  9. washthe organic phase was washed with water
  10. dry with materialThe solution was dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography (2% MeOH:DCM)

Sources & evidence

ORD record
ord-07be02dda01e4827909f118dc193f26c
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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