Water → 1-(1-Methylethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

HRID 244742Notes

Reaction equation

HRID 244742 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:16][CH:17]=[CH:18][C:11]=12.[CH3:19][CH:20]([N:22]1[C:26]([C:27]([NH:29][C:30]2[C:31]3[C:35]([CH:36]=[C:37](B4OC(C)(C)CC(C)(C)O4)[CH:38]=2)=[N:34][N:33](C2CCCCO2)[CH:32]=3)=[O:28])=[CH:25][CH:24]=[N:23]1)[CH3:21].O>O1CCOCC1>[CH3:21][CH:20]([N:22]1[C:26]([C:27]([NH:29][C:30]2[CH:38]=[C:37]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]4[NH:16][CH:17]=[CH:18][C:11]=34)[CH:36]=[C:35]3[C:31]=2[CH:32]=[N:33][NH:34]3)=[O:28])=[CH:25][CH:24]=[N:23]1)[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 222736434-Bromo-1H-pyrrolo[2,3-b]pyridineHCID 582557371-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Product 1

HCID 583563491-(1-Methylethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with Solvias catalyst (7 mg), tripotassium phosphate (84 mg) and 4-bromo-1H-pyrrolo[2,3-b]pyridine (commercial from Sinova, 29 mg). 1-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide (65 mg) in 1,4-dioxane (0.5 ml) was added, followed by water (0.1 ml) and the reaction was heated under microwave irradiation for 10 min at 120° C. The reaction was washed through a silica cartridge, preconditioned with methanol, with methanol. The solvent was removed under a stream of nitrogen, then washed with DCM and water. The resultant solution was evaporated under a stream of nitrogen. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (method A). Appropriate fractions were dried under a stream of nitrogen. The residue was dissolved in methanol, 2 M HCl (aq) (3 drops) was added and the solution was left to stand for 30 min. The solvent was removed under a stream of nitrogen and the residue was dissolved in methanol, washed with methanol through an aminopropyl cartridge preconditioned with methanol and dried under a stream of nitrogen to give title compound, 20 mg.

Workup

  1. washThe reaction was washed through a silica cartridge
  2. customThe solvent was removed under a stream of nitrogen
  3. washwashed with DCM and water
  4. customThe resultant solution was evaporated under a stream of nitrogen
  5. dissolutionThe residue was dissolved in DMSO
  6. custommethanol (1 ml, 1:1, v/v) and purified by MDAP (method A)
  7. customAppropriate fractions were dried under a stream of nitrogen
  8. dissolutionThe residue was dissolved in methanol
  9. addition2 M HCl (aq) (3 drops) was added
  10. waitthe solution was left
  11. customThe solvent was removed under a stream of nitrogen
  12. dissolutionthe residue was dissolved in methanol
  13. washwashed with methanol through an aminopropyl cartridge
  14. customdried under a stream of nitrogen

Sources & evidence

ORD record
ord-2eb47b792d1e488c8661fd4317876eff
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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