Water → HCID 118114036, compound

HRID 706518Notes

Reaction equation

HRID 706518 reaction equation
I[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([NH2:11])[N:8]([CH:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)=[C:16]([O:32][CH3:33])[CH:15]=3)[CH3:13])[C:5]2=[N:6][CH:7]=1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCCC1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[CH3:33][O:32][C:16]1[CH:15]=[C:14]([CH:12]([N:8]2[C:5]3=[N:6][CH:7]=[C:2]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)[CH:3]=[C:4]3[N:10]=[C:9]2[NH2:11])[CH3:13])[CH:19]=[CH:18][C:17]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118113993HCID 118113993, compound

Product 1

HCID 118114036HCID 118114036, compoundYield 136.1%

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred mixture of 6-iodo-3-(1-(3-methoxy-4-((4-(trifluoromethyl)benzyl)oxy)phenyl)ethyl)-3H-imidazo[4,5-b]pyridin-2-amine (0.253 g, 0.45 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.158 g, 0.76 mmol), potassium phosphate tribasic (0.495 g, 2.29 mmol) in tetrahydrofuran (5 mL)/water (4 mL) was added 2nd generation XPhos precatalyst (0.032 g, 0.041 mmol). The yellow solution was degassed under vacuum/backfilled with nitrogen (×3). The mixture heated to 75° C. After 4 h, the mixture was allowed to cool to room temperature and was diluted with water (40 mL). The mixture was extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 0.320 g of a brown oil. Chromatographic purification (CombiFlash, 12 g SiO2 gold column, 1-5% 2M ammonia in methanol/dichloromethane elute) afforded 0.178 g (77%) of the product as a tan solid:

Workup

  1. customThe yellow solution was degassed under vacuum/backfilled with nitrogen (×3)
  2. temperatureto cool to room temperature
  3. additionwas diluted with water (40 mL)
  4. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3f9f17aee9c64a279dfd840f5b1c5bc3
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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