Potassium Carbonate → 1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-4-nitro-1H-indazole

HRID 79483Notes

Reaction equation

HRID 79483 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)[C:19](Br)=[N:18]2)=[N:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:30]1(B(O)O)[CH2:32][CH2:31]1.C([O-])([O-])=O.[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+]>C(O[Pd]OC(=O)C)(=O)C.O1CCOCC1.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)[C:19]([CH:30]3[CH2:32][CH2:31]3)=[N:18]2)=[N:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateHCID 672601791-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole

Product 1

HCID 672611071-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-4-nitro-1H-indazole

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A first flask was charged with 1,4-dioxane/H2O (50 mL/10 mL). The flask was cooled to 0° C. and vacuum was applied for 20 minutes. A second flask was charged with 1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole (6.07 g, 13.4 mmol), cyclopropylboronic acid (4.60 g, 53.6 mmol), diacetoxypalladium (0.150 g, 0.670 mmol), K2CO3 (5.55 g, 40.2 mmol) and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (0.686 g, 1.34 mmol). The second flask was also evacuated with vacuum and back filled with N2 for 3 times. The cold degassed dioxane/H2O was added to the second flask, which was evacuated with vacuum and back filled with argon for 5 times. The reaction mix was then heated to 80° C. for 3 hours. A sample (1H NMR) taken from the flask showed complete reaction at this point. The reaction was cooled to ambient temperature, filtered and concentrated under reduced pressure. The residue was diluted with EtOAc (200 mL). The organic layer was washed with saturated NaHCO3, dried (Na2SO4) and concentrated to give desired product, which was used in the next step without further purification.

Workup

  1. customThe second flask was also evacuated with vacuum
  2. additionback filled with N2 for 3 times
  3. customThe cold degassed dioxane/H2O
  4. additionwas added to the second flask, which
  5. customwas evacuated with vacuum
  6. additionback filled with argon for 5 times
  7. additionThe reaction mix
  8. temperaturewas then heated to 80° C. for 3 hours
  9. customreaction at this point
  10. temperatureThe reaction was cooled to ambient temperature
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. additionThe residue was diluted with EtOAc (200 mL)
  14. washThe organic layer was washed with saturated NaHCO3
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-cdadfd5a8d8b40fcb37fc3ab20359451
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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