Potassium Phosphate, Tribasic → 7-Pyridin-4-yl-imidazo[1,2-a]pyridine

HRID 1446665Notes

Reaction equation

HRID 1446665 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.[N:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O1CCOCC1.O>[N:11]1[CH:16]=[CH:15][C:14]([C:2]2[CH:7]=[CH:6][N:5]3[CH:8]=[CH:9][N:10]=[C:4]3[CH:3]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 196959017-Chloroimidazo(1,2-a)pyridine

Product 1

HCID 685456367-Pyridin-4-yl-imidazo[1,2-a]pyridineYield 89%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

Charge a 250 mL round bottom flask equipped with a magnetic stirrer, temperature controlled heating mantle, under N2 atmosphere, condenser, with 7-chloro-imidazo[1,2-a]pyridine (4.0 g, 26.2 mmol), 4-pyridyl boronic acid (3.54 g, 28.8 mmol 1.1 Eq), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (600 mg) [X-Phos can be used as an alternate ligand in this reaction], Pd(OAc)2 (145 mg), K3PO4 (11.1 g, 52.6 mmol), and dioxane: H2O 2:1 (170 mL). Warm the reaction while purging with a N2 needle, then heat to 65° C. for 18 hours. Cool the reaction to room temperature and transfer to a separatory funnel and siphon off the bottom layer (25 mL). Add EtOAc and evaporate the solvents under reduced pressure off. Take the solids up into EtOAc again, and evaporate under reduced pressure to azeotrope off traces of water. Dissolve the brown solid into CH2Cl2 and 5% MeOH and then chromatograph using SiO2 eluting with a slow gradient of 0% to 10% of 2 M NH3 in MeOH with the balance CH2Cl2. Evaporate the product fractions under reduced pressure to give a light yellow/tan solid 4.5 g (89%). MS (ES), m/z 196 (M+1).

Workup

  1. additionCharge a 250 mL round bottom flask
  2. customequipped with a magnetic stirrer
  3. temperaturetemperature controlled heating mantle
  4. temperatureWarm
  5. customthe reaction
  6. customwhile purging with a N2 needle
  7. temperatureCool
  8. customthe reaction to room temperature
  9. customAdd EtOAc and evaporate the solvents under reduced pressure off
  10. customevaporate under reduced pressure
  11. dissolutionDissolve the brown solid into CH2Cl2 and 5% MeOH
  12. customEvaporate the product fractions under reduced pressure

Sources & evidence

ORD record
ord-aa1a7ded868946db80d9fe14d8d41971
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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