Potassium Phosphate, Tribasic → HCID 68538863, compound

HRID 1446667Notes

Reaction equation

HRID 1446667 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]3[CH:20]=[CH:21][C:22](Cl)=[CH:23][C:18]3=[N:17][CH:16]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][N:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]3[CH:20]=[CH:21][C:22]([C:30]4[CH:29]=[N:28][C:27]([F:26])=[CH:32][CH:31]=4)=[CH:23][C:18]3=[N:17][CH:16]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 68543013HCID 68543013, compound

Product 1

HCID 68538863HCID 68538863, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Suspend [4-(7-chloro-imidazo[1,2-a]pyridin-3-yl)-benzyl]-carbamic acid tert-butyl ester (1.90 g, 5.30 mmol, 1.0 eq.) in dioxane/water (2:1, 36 mL). Add 2-fluoro-5-pyridine boronic acid (0.75 g, 5.30 mmol, 1.0 eq.), K3PO4 (2.25 g, 10.6 mmol, 2.0 eq.), and S-phos (0.272 g, 0.66 mmol, 0.125 eq.). Deoxygenate the mixture and fill with nitrogen. Add Pd(OAc)2 (0.059 g, 0.265 mmol, 0.05 eq.). Deoxygenate the reaction mixture and fill with nitrogen. Stir the reaction at 80° C. under nitrogen for 16 hours. A white solid is formed after the solution is cooled down. Filter off the white solid, wash with water (3×15 mL), EtOAc (3×15 mL). Collect the solid (1.50 g). Purify the filtrate by silica gel flash chromatography with a 0-5% MeOH/DCM gradient to afford the title compound (0.52 g) as a slightly yellow solid. Combine the chromatography product and the filtered solids to give slightly yellow solid. (2.02 g, 4.83 mmol) MS(ES), m/z 419 (M+1).

Workup

  1. customDeoxygenate the mixture and fill with nitrogen
  2. customDeoxygenate the reaction mixture
  3. customthe reaction at 80° C. under nitrogen for 16 hours
  4. customA white solid is formed after the solution
  5. temperatureis cooled down
  6. filtrationFilter off the white solid
  7. washwash with water (3×15 mL), EtOAc (3×15 mL)
  8. customCollect the solid (1.50 g)
  9. customPurify the filtrate by silica gel flash chromatography with a 0-5% MeOH/DCM gradient

Sources & evidence

ORD record
ord-7604818caacd47f8bc1cfdd1423e4140
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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