Sodium Bicarbonate → N-Phenyl-N'-{4-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1-(tetrahydro-2-furanylmethyl)-1H-pyrazol-3-yl]phenyl}urea

HRID 1821185Notes

Reaction equation

HRID 1821185 reaction equation
Br[C:2]1[C:3]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:21])=[CH:15][CH:14]=2)=[N:4][N:5]([CH2:7][CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[CH:6]=1.C1(S([N:38]2[C:42]3=[N:43][CH:44]=[CH:45][C:46](B4OC(C)(C)C(C)(C)O4)=[C:41]3[CH:40]=[CH:39]2)(=O)=O)C=CC=CC=1.C(=O)(O)[O-].[Na+]>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.CN(C)C=O>[C:23]1([NH:22][C:20]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([C:3]3[C:2]([C:46]4[CH:45]=[CH:44][N:43]=[C:42]5[NH:38][CH:39]=[CH:40][C:41]=45)=[CH:6][N:5]([CH2:7][CH:8]4[CH2:12][CH2:11][CH2:10][O:9]4)[N:4]=3)=[CH:14][CH:15]=2)=[O:21])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 450745461-(Benzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 68996099HCID 68996099, compound

Product 1

HCID 57398440N-Phenyl-N'-{4-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1-(tetrahydro-2-furanylmethyl)-1H-pyrazol-3-yl]phenyl}ureaYield 11%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-{4-[4-bromo-1-(tetrahydro-2-furanylmethyl)-1H-pyrazol-3-yl]phenyl}-N′-phenylurea (0.147 mmol), 1-(phenylsulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (0.162 mmol), N,N-dimethylformamide (1.5 mL), saturated aqueous sodium bicarbonate (0.44 mL) and tetrakis(triphenylphosphine)palladium(0) (0.007 mmol) in a sealed tube was stirred at 100° C. for 18 hrs. The solution was cooled to room temperature, filtered though Celite and concentrated in vacuo. The residue was dissolved in methanol (5 mL) and 6.0N aqueous sodium hydroxide (1 mL) and stirred at 70° C. for 6 h. The reaction mixture was concentrated in vacuo, dissolved in water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by Gilson reverse phase HPLC afforded the title compound as a white solid (11%). ESMS [M+H]+: 479.4

Workup

  1. temperatureThe solution was cooled to room temperature
  2. filtrationfiltered though Celite
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in methanol (5 mL)
  5. stirring6.0N aqueous sodium hydroxide (1 mL) and stirred at 70° C. for 6 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. dissolutiondissolved in water (10 mL)
  8. extractionextracted with ethyl acetate (3×10 mL)
  9. dry with materialThe combined organic extracts were dried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by Gilson reverse phase HPLC

Sources & evidence

ORD record
ord-8658ae2ea64a42f2aa4d3493e4989ca2
Source dataset
uspto-grants-2009_10
Patent number
US07605266B2

Reaction notes

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