Acetonitrile → 1-Butyl-3-[4-fluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl]-urea

HRID 1964923Notes

Reaction equation

HRID 1964923 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[CH:14]=[C:15]([NH:20][C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.C(#N)C>C(=O)([O-])[O-].[K+].[K+].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>[CH2:24]([NH:23][C:21]([NH:20][C:15]1[CH:16]=[CH:17][C:18]([F:19])=[C:13]([C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:30]4[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=4)[CH:3]=3)[NH:8][CH:9]=2)=[O:12])[CH:14]=1)=[O:22])[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 27343783-Pyridinylboronic acidHCID 58086051HCID 58086051, compound

Product 1

HCID 580863551-Butyl-3-[4-fluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl]-ureaYield 61%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

To 1-[3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-4-fluoro-phenyl]-3-butyl-urea (P-1637, 14.0 mg, 0.0000323 mol), 3-pyridylboronic acid (5.96 mg, 0.0000485 mol), and Tetrakis(triphenylphosphine)palladium(0) (0.820 mg, 7.09E-7 mol) were mixed in 1.00 M potassium carbonate in water (1.00 mL) and acetonitrile (2.00 mL, 0.0353 mol). The resulting mixture was heated at 120° C. in the microwave for 40 minutes. The reaction was extracted with ethyl acetate and water twice, and the combined organic layers were washed with 1M sodium bicarbonate followed by brine and the organic layer was dried over magnesium sulfate and filtered. The organic layer was concentrated and purified by reverse phase HPLC (acetonitrile and water with 0.1% formic acid) to give the compound as a white solid (P-1637, 8.5 mg, 61%). MS(ESI) [M+H+]+=432.3.

Workup

  1. extractionThe reaction was extracted with ethyl acetate and water twice
  2. washthe combined organic layers were washed with 1M sodium bicarbonate
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe organic layer was concentrated
  6. custompurified by reverse phase HPLC (acetonitrile and water with 0.1% formic acid)

Sources & evidence

ORD record
ord-10b3c4f90db9412da7fe35ff59b46005
Source dataset
uspto-grants-2013_04
Patent number
US08415469B2

Reaction notes

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