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

HRID 244743Notes

Reaction equation

HRID 244743 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:15]=[N:14][CH: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]=[N:14][CH: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 125100554-Bromo-1H-pyrrolo(2,3-c)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 583563861-(1-Methylethyl)-N-[6-(1H-pyrrolo[2,3-c]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-c]pyridine (from prep such as in US2005/0090529, 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 a total of 30 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, 2M HCl (aq) (3 drops) was added and the solution was left to stand for 60 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, 5 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. addition2M 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-6f039d9b7bcb442e8c4cfdf6267e31d0
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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