Sodium Bicarbonate → 2-Aminocarbonylamino-6-(4-hydroxymethylpyridin-2-yl)indole-3-carboxamide

HRID 216627Notes

Reaction equation

HRID 216627 reaction equation
[NH2:1][C:2]([NH:4][C:5]1[NH:6][C:7]2[C:12]([C:13]=1[C:14](=[O:16])[NH2:15])=[CH:11][CH:10]=[C:9](B1OC(C)(C)C(C)(C)O1)[CH:8]=2)=[O:3].C(=O)([O-])O.[Na+].Br[C:32]1[CH:37]=[C:36]([CH2:38][OH:39])[CH:35]=[CH:34][N:33]=1>O.O1CCOCC1.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]([NH:4][C:5]1[NH:6][C:7]2[C:12]([C:13]=1[C:14]([NH2:15])=[O:16])=[CH:11][CH:10]=[C:9]([C:32]1[CH:37]=[C:36]([CH2:38][OH:39])[CH:35]=[CH:34][N:33]=1)[CH:8]=2)=[O:3]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 14512957(2-Bromopyridin-4-yl)methanolHCID 591897502-Aminocarbonylamino-3-carbamoylindole-6-boronic acid pinacol ester2×

Product 1

HCID 591899142-Aminocarbonylamino-6-(4-hydroxymethylpyridin-2-yl)indole-3-carboxamideYield 23.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)SolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A solution mixture of 2-aminocarbonylamino-3-carbamoylindole-6-boronic acid pinacol ester (Compound 6-1, 90 mg, 0.26 mmol), sodium hydrogen carbonate (55 mg, 0.65 mmol), 2-bromopyridine-4-methanol (58 mg, 0.31 mmol) and tetrakis(triphenylphosphine)palladium (0) (15 mg, 0.013 mmol) in water-1,4-dioxane (1:3, 15 mL) was stirred at 100° C. for 6 hours. Brine (5 mL) was added to the reaction mixture, and the whole was extracted with ethyl acetate (5 mL). The organic layer was dried over anhydrous magnesium sulfate, and was filtered throught Celite® pad. After the solvent was evaporated under reduced pressure, the resultant solid was washed with ethanol (2 mL), and dried under reduced pressure to give the title compound (20 mg) as a brown solid (yield 23%).

Workup

  1. extractionthe whole was extracted with ethyl acetate (5 mL)
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationwas filtered
  4. customAfter the solvent was evaporated under reduced pressure
  5. washthe resultant solid was washed with ethanol (2 mL)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-254dc5bafe4a48ddaa493831133fd402
Source dataset
uspto-grants-2012_06
Patent number
US08193237B2

Reaction notes

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