Potassium Phosphate, Tribasic → HCID 91801232, compound

HRID 706418Notes

Reaction equation

HRID 706418 reaction equation
Br[C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)=[C:13]([O:27][CH3:28])[CH:12]=3)[C:7]([NH2:9])=[N:8][C:4]=2[CH:3]=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH3:28][O:27][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[O:17][CH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=1)[CH2:10][N:6]1[C:5]2[CH:29]=[CH:30][C:2]([C:35]3[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=3)=[CH:3][C:4]=2[N:8]=[C:7]1[NH2:9]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118114043HCID 118114043, compound

Product 1

HCID 91801232HCID 91801232, compoundYield 119.1%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
125 °C

Procedure

To a stirred suspension of 5-bromo-1-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-1H-benzo[d]imidazol-2-amine (0.28 g, 0.59 mmol) in 1,4-dioxane (8 mL) and water (6 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.15 g, 0.73 mmol), potassium phosphate (0.44 g, 2.06 mmol), tricyclohexylphosphine (0.016 g, 0.059 mmol), and palladium(II)acetate (0.007 g, 0.029 mmol). The reaction mixture was heated to 125° C. in a microwave reactor. After 15 min, the reaction mixture was diluted with water. The mixture was extracted with ethyl acetate (×3), and the combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated to provide 0.33 g of a light green solid. Chromatographic purification (Combi-Flash, 12 g SiO2 gold column, 1-5% 2 M ammonia in methanol/dichloromethane elute) afforded 0.13 g (48%) of the product as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ 7.96 (s, 1H), 7.71 (s, 1H), 7.34-7.24 (m, 3H), 7.05-6.87 (m, 6H), 6.65-6.60 (m, 1H), 6.50 (s, 2H), 5.11 (s, 2H), 4.90 (s, 2H), 3.81 (s, 3H), 3.72 (s, 3H), 3.69 (s, 3H) ppm; (M+1) 470.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (×3)
  2. washthe combined organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7d6e02d7b7694535a82033046572818f
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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