Water → HCID 66837119, compound

HRID 2277107Notes

Reaction equation

HRID 2277107 reaction equation
Br[C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1B(O)O.O>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.COCCOC>[CH3:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1[C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 112525844-Bromo-1H-benzimidazole

Product 1

HCID 66837119HCID 66837119, compoundYield 62.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A vial was charged with tetrakis(triphenylphosphine)palladium(0) (0.129 g, 0.112 mmol), 4-bromo-1H-benzo[d]imidazole (0.200 g, 1.015 mmol), sodium carbonate (0.430 g, 4.06 mmol), and 4-methylpyridin-3-ylboronic acid (0.146 g, 1.066 mmol). The mixture was stirred at room temperature for 10 min under N2, then water (1.894 mL), DME (3.79 mL), and EtOH (1.894 mL) were added sequentially. The resultant mixture was stirred under N2 for 15 min, then heated at 90° C. overnight. After 21.5 h, the reaction mixture was allowed to cool to room temperature, then quenched with water and diluted with EtOAc. The layers were separated and the aqueous phase extracted with EtOAc (3×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a brown residue. The crude material was dissolved in a minimal amount of CH2Cl2 and chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 1-20% MeOH in CH2Cl2 over 30 min, tr=20 min) gave the title compound (132 mg, 0.631 mmol, 62.1% yield) as a white foam. ESI MS (M+H)+=210.0. HPLC Peak tr=14.20 minutes. Purity >99%. HPLC conditions: Xbridge Phenyl column, 4.6×150 mm. 30 min gradient (10-100% B), 2 mL/min, 23° C. @ 220 nm, Solvent A: 10 mM NH4HCO3 pH 9.5 in H2O:MeOH (95:5), Solvent B: 10 mM NH4HCO3 pH 9.5 in H2O:MeOH (5:95).

Workup

  1. temperatureheated at 90° C. overnight
  2. waitAfter 21.5 h
  3. temperatureto cool to room temperature
  4. customquenched with water
  5. additiondiluted with EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous phase extracted with EtOAc (3×)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a brown residue
  12. customchromatographed
  13. customPurification of the crude material by silica gel chromatography
  14. customan ISCO machine (40 g column, 40 mL/min, 1-20% MeOH in CH2Cl2 over 30 min, tr=20 min)

Sources & evidence

ORD record
ord-9bba6c666a8f42568f60c8885488c3ba
Source dataset
uspto-grants-2015_09
Patent number
US09133160B2

Reaction notes

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