Potassium Phosphate, Tribasic → HCID 118114341, compound

HRID 706526Notes

Reaction equation

HRID 706526 reaction equation
I[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH:19]([C:21]4[CH:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)[CH3:20])=[C:14]([O:29][CH3:30])[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[O-:31]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:39][N:40]1[CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:42]=[N:41]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.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].O>[CH:30]([OH:29])=[O:31].[CH3:30][O:29][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[O:18][CH:19]([C:21]1[CH:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)[CH3:20])[CH2:11][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:43]3[CH:42]=[N:41][N:40]([CH3:39])[CH:44]=3)[CH:3]=[C:4]2[N:10]=[CH:9]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118113997HCID 118113997, compound

Product 1

HCID 118114341HCID 118114341, compoundYield 50.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred suspension of 6-iodo-3-(3-methoxy-4-(1-(6-methoxypyridin-3-yl)ethoxy)benzyl)-3H-imidazo[4,5-b]pyridine (0.200 g, 0.39 mmol), potassium phosphate tribasic (0.164 g, 0.77 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.100 g, 0.48 mmol) and tricyclohexylphosphine (0.008 g, 0.028 mmol) in 1,4-dioxane (3 mL)/water (1.5 mL) was added tris(dibenzylideneacetone)dipalladium(0) (0.012 g, 0.013 mmol). The mixture was degassed by bubbling nitrogen through the mixture for 2 min, and then the mixture was irradiated in a microwave reactor at 120° C. After 30 min, the mixture was allowed to cool to room temperature and was filtered through Celite. The filtrate was subjected to direct purification (50 g C18 column, water/acetonitrile/0.1% formic acid elute) to provide an impure material. A second purification under the same conditions afforded 0.051 g (26%) of the product as a white solid: 1H NMR (400 MHz, CD3OD) δ 8.62 (d, J=1.9 Hz, 1H), 8.37 (s, 1H), 8.20-8.13 (m, 1H), 8.05 (dd, J=7.6, 1.6 Hz, 2H), 7.90 (d, J=0.8 Hz, 1H), 7.71 (dd, J=8.6, 2.5 Hz, 1H), 7.05 (d, J=1.9 Hz, 1H), 6.83-6.69 (m, 3H), 5.42 (s, 2H), 5.37 (q, J=6.4 Hz, 1H), 3.95 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 1.58 (d, J=6.4 Hz, 3H) ppm; (M+1)=471.

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen through the mixture for 2 min
  3. customthe mixture was irradiated in a microwave reactor at 120° C
  4. filtrationwas filtered through Celite
  5. customThe filtrate was subjected to direct purification (50 g C18 column, water/acetonitrile/0.1% formic acid elute)
  6. customto provide an impure material
  7. customA second purification under the same conditions

Sources & evidence

ORD record
ord-3fc6cc62d3d645398841c92f2df61d41
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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