Sodium t-butoxide → 4-[4-Methyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-4-ylamino)-phenylsulfanyl]-phenol

HRID 607156Notes

Reaction equation

HRID 607156 reaction equation
Cl[C:2]1[C:3]2[C:4](=[N:8][N:9]([CH3:11])[CH:10]=2)[N:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=1[S:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:19][C:17]1[CH:16]=[CH:15][C:14]([S:20][C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[C:13]([NH:12][C:2]2[C:3]3[C:4](=[N:8][N:9]([CH3:11])[CH:10]=3)[N:5]=[CH:6][CH:7]=2)[CH:18]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 668081234-(2-Amino-4-methyl-phenylsulfanyl)-phenolHCID 668084904-Chloro-2-methyl-2H-pyrazolo[3,4-b]pyridine

Product 1

HCID 250106674-[4-Methyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-4-ylamino)-phenylsulfanyl]-phenolYield 21%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Procedure

A mixture of the product of Example 8c (62.1 mg, 0.371 mmol), the product of Example 6c (85.7 mg, 0.371 mmol), Pd2(dba)3 (16.9 mg, 0.0185 mmol), sodium t-butoxide (89.0 mg, 0.926 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (25.4 mg, 0.0741 mmol) in toluene (3 mL) was degassed, left under a positive pressure of nitrogen, and heated under reflux for 2 h. Additional amounts of Pd2(dba)3 (7.0 mg, 0.0076 mmol) and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (15 mg, 0.044 mmol) were added the reaction mixture was heated under reflux for an addition 2 h. The mixture was then cooled to room temperature and partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a 2-5% MeOH/CH2Cl2, gradient to provide the title compound (0.0279 g, 21% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 2.27 (s, 3H), 4.11 (s, 3H), 5.92 (d, J=5.15 Hz, 1H), 6.75-6.85 (m, 3H), 7.02 (dd, J=8.27, 0.92 Hz, 1H), 7.14 (s, 1H), 7.18-7.27 (m, 2H), 8.09 (d, J=5.15 Hz, 1H), 8.20 (s, 1H), 8.77 (s, 1H), 9.82 (s, 1H); MS (ESI+) m/z 363.0 (M+H)+ (ESI−) m/z 360.9 (M−H)−.

Workup

  1. waitleft under a positive pressure of nitrogen
  2. temperatureheated
  3. temperatureunder reflux for 2 h
  4. temperaturewas heated
  5. temperatureunder reflux for an addition 2 h
  6. custompartitioned between ethyl acetate (30 mL) and water (30 mL)
  7. extractionThe aqueous phase was extracted with ethyl acetate
  8. washthe combined organic phase was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe residue was purified by chromatography on silica gel
  13. washeluting with a 2-5% MeOH/CH2Cl2, gradient

Sources & evidence

ORD record
ord-a543db252a8944a28187912b636f3db4
Source dataset
uspto-grants-2011_03
Patent number
US07915411B2

Reaction notes

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