Potassium Phosphate, Tribasic → GZ 389988)

HRID 706445Notes

Reaction equation

HRID 706445 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([NH2:11])[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)=[C:15]([O:29][CH3:30])[CH:14]=3)[C:5]2=[N:6][CH:7]=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH3:30][O:29][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[O:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)[CH2:12][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:35]3[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=3)[CH:3]=[C:4]2[N:10]=[C:9]1[NH2:11]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118114051HCID 118114051, compound

Product 1

HCID 118009787GZ 389988)Yield 144.4%

Reagents, catalysts & solvents 4

HCID 75806TricyclohexylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred solution of 6-bromo-3-(3-methoxy-4-(4-methoxybenzyloxyl)benzyl)-3H-imidazo[4,5-b]pyridin-2-amine (0.25 g, 0.53 mmol) in 1,4-dioxane (10 mL) and water (4 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.14 g, 0.66 mmol), potassium phosphate tribasic (0.39 g, 1.84 mmol), tricyclohexylphosphine (0.015 g, 0.052 mmol), palladium(II) acetate (0.005 g, 0.026 mmol). The reaction mixture heated to 125° C. in a microwave reactor. After 15 min, the reaction mixture was allowed to cool to room temperature and was diluted with water. The mixture was extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated to provide 0.36 g of a greenish brown solid. Chromatographic purification (Combi-Flash, 12 g SiO2 gold column, 1-10% 2M ammonia in methanol/dichloromethane) afforded 0.10 g (41%) of the product as a light green solid: 1H NMR (400 MHz, DMSO-d6) δ 8.12-8.08 (m, 2H), 7.83 (d, J=0.6 Hz, 1H), 7.58 (d, J=1.9 Hz, 1H), 7.32 (d, J=8.7 Hz, 2H), 7.08 (d, J=1.9 Hz, 1H), 6.96-6.85 (m, 5H), 6.72 (dd, J=8.3, 1.9 Hz, 1H), 5.18 (s, 2H), 4.92 (s, 2H), 3.85 (s, 3H), 3.74 (s, 3H), 3.70 (s, 3H) ppm, (M+1)=471.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted twice with ethyl acetate
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5c1dd2bef07747c193d56c34958e19ec
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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