Water → 1-(1-Methylethyl)-N-[6-(2-oxo-2,3-dihydro-1,3-benzoxazol-7-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

HRID 244745Notes

Reaction equation

HRID 244745 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[C:18]2[O:17][C:16](=[O:19])[NH:15][C:14]=2[CH:13]=[CH:12][CH:11]=1.[CH3:20][CH:21]([N:23]1[C:27]([C:28]([NH:30][C:31]2[C:32]3[C:36]([CH:37]=[C:38](B4OC(C)(C)CC(C)(C)O4)[CH:39]=2)=[N:35][N:34](C2CCCCO2)[CH:33]=3)=[O:29])=[CH:26][CH:25]=[N:24]1)[CH3:22].O>O1CCOCC1.CO>[CH3:22][CH:21]([N:23]1[C:27]([C:28]([NH:30][C:31]2[CH:39]=[C:38]([C:10]3[C:18]4[O:17][C:16](=[O:19])[NH:15][C:14]=4[CH:13]=[CH:12][CH:11]=3)[CH:37]=[C:36]3[C:32]=2[CH:33]=[N:34][NH:35]3)=[O:29])=[CH:26][CH:25]=[N:24]1)[CH3:20]

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 115575587-Bromobenzo[d]oxazol-2(3H)-oneHCID 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 583564261-(1-Methylethyl)-N-[6-(2-oxo-2,3-dihydro-1,3-benzoxazol-7-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with Solvias catalyst (8 mg), tripotassium phosphate (90 mg) and 7-bromo-1,3-benzoxazol-2(3H)-one (from prep. such as US2006/0122189A1, 33 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 (70 mg) in 1,4-dioxane (0.5 ml) was added followed by water (0.1 ml). The reaction was heated under microwave irradiation at 120° C. for 10 min. The reaction was passed through a silica cartridge preconditioned with methanol, washing with methanol, then dried under a stream of nitrogen. The residue was subjected to a DCM/water wash and then dried 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 evaporated under a stream of nitrogen. The residues were dissolved in a minimum amount of methanol and combined. A few drops of 2M HCl (aq) were added and the reaction was left to stand at room temperature. The reaction was then evaporated under a stream of nitrogen, passed through an aminopropyl cartridge and dried to give title compound, 10 mg.

Workup

  1. washwashing with methanol
  2. customdried under a stream of nitrogen
  3. washwash
  4. customdried 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 evaporated under a stream of nitrogen
  8. dissolutionThe residues were dissolved in a minimum amount of methanol
  9. additionA few drops of 2M HCl (aq) were added
  10. waitthe reaction was left
  11. customto stand at room temperature
  12. customThe reaction was then evaporated under a stream of nitrogen
  13. customdried

Sources & evidence

ORD record
ord-befc2fce4ee8422a8bd10e6b95c4cda3
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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