Water → HCID 178432258, compound

HRID 74452Notes

Reaction equation

HRID 74452 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[NH:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([OH:28])[CH:22]=2)=[O:18].[O:29]1[CH2:32][CH:31](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:30]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[NH:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([O:28][CH:31]1[CH2:32][O:29][CH2:30]1)[CH:22]=2)=[O:18]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 13153907Oxetan-3-yl 4-methylbenzene-1-sulfonateHCID 178432259[5-Amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(6-hydroxy-1H-indol-2-yl)-methanone

Product 1

HCID 178432258HCID 178432258, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

[5-Amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(6-hydroxy-1H-indol-2-yl)-methanone (21 mg, 0.056 mmol), toluene-4-sulfonic acid oxetan-3-yl ester (19 mg, 0.084 mmol), and potassium carbonate (13 mg, 0.095 mmol) were dissolved in anhydrous N,N-dimethylformamide (DMF), and heated at 80° C. with stirring under a nitrogen atmosphere for six days. After cooling to room temperature, the reaction mixture was combined with water, and extracted with an ethyl acetate/methanol (10/1) solution. The organic layer was isolated, washed with water, and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol=100/3) to give [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-(oxetan-3-yloxy)-1H-indol-2-yl]-methanone as a yellow solid (6.9 mg, 29%).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with an ethyl acetate/methanol (10/1) solution
  3. customThe organic layer was isolated
  4. washwashed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe desiccant was removed by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (dichloromethane/methanol=100/3)

Sources & evidence

ORD record
ord-0ff164d02e6f4b0aa1c76bffd466356b
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Reaction notes

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