Sodium Hydroxide → HCID 11199788, compound

HRID 734673Notes

Reaction equation

HRID 734673 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10]([CH3:16])=[C:9]2[C:17]([O:19]C)=O)=[CH:4][CH:3]=1.[OH-].[Na+].[NH:23]1[C:31]2[C:26](=[CH:27][C:28]([NH2:32])=[CH:29][CH:30]=2)[CH:25]=[N:24]1.N=C=N>CO.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10]([CH3:16])=[C:9]2[C:17]([NH:32][C:28]2[CH:27]=[C:26]3[C:31](=[CH:30][CH:29]=2)[NH:23][N:24]=[CH:25]3)=[O:19])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 880121H-Indazol-5-amineHCID 160435CarbodiimideHCID 5306295HCID 5306295, compound

Product 1

HCID 11199788HCID 11199788, compoundYield 0.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

The product of Step 1 (1.58 g, 5.70 mmol, 1 equiv) was dissolved in methanol (24 mL) and 2.5 N NaOH (8 mL) was added. The reaction was heated to 60° C. for 3 h. Upon cooling, the resulting mixture was partitioned between EtOAc and water. The aqueous layer was acidified to pH 1 and extracted with EtOAc. The phases were separated and the organic phase was concentrated in vacuo. The resulting residue (1.50 g, 5.70 mmol, 1.1 equiv) was dissolved in DMF (30 mL). 1H-indazol-5-amine (700 mg, 5.18 mmol, 1.0 equiv) and PS-carbodiimide resin (8.27 g, 7.77 mmol, 1.5 equiv) were added and the mixture stirred overnight at room temperature. The resin was removed by filtration and washed alternately with methanol and CH2Cl2, followed by diethyl ether. The filtrate was concentrated en vacuo to remove the volatile solvents. The residue was dissolved in EtOAc, washed twice with water and once with satd. NaHCO3. The organic phase was concentrated in vacuo and the residue was purified by reverse phase HPLC (Xterra Prep 19×50, 25 mL/min, 10-90% 5 mM aq. NH4HCO3/CH3CN over 9 minutes) to provide 8 mg (0.4%) of a white crystalline solid. MS (ES+) m/e 379 [M+H]+.

Workup

  1. temperatureUpon cooling
  2. customthe resulting mixture was partitioned between EtOAc and water
  3. extractionextracted with EtOAc
  4. customThe phases were separated
  5. concentrationthe organic phase was concentrated in vacuo
  6. customThe resin was removed by filtration
  7. washwashed alternately with methanol and CH2Cl2
  8. concentrationThe filtrate was concentrated en vacuo
  9. customto remove the volatile solvents
  10. dissolutionThe residue was dissolved in EtOAc
  11. washwashed twice with water and once with satd
  12. concentrationThe organic phase was concentrated in vacuo
  13. customthe residue was purified by reverse phase HPLC (Xterra Prep 19×50, 25 mL/min, 10-90% 5 mM aq. NH4HCO3/CH3CN over 9 minutes)

Sources & evidence

ORD record
ord-3d50abfd31074f32a96aefba72d73946
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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