Potassium Phosphate, Tribasic → HCID 86676943, compound

HRID 2284366Notes

Reaction equation

HRID 2284366 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.O1CCOCC1>[Cl:8][C:6]1[CH:7]=[C:2]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:13]=2[CH3:12])[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27627114-Methylpyridine-3-Boronic AcidHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 1

HCID 86676943HCID 86676943, compoundYield 34.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A microwave vial was charged with a mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (1.1 g, 4.73 mmol), 4-methylpyridin-3-ylboronic acid (0.648 g, 4.73 mmol), tetrakis(triphenylphosphine)palladium(0) (0.547 g, 0.473 mmol), dioxane (14 mL), and K3PO4 (7.10 mL, 14.20 mmol) (2.0 M water solution) was stirred at room temperature for 5 min. under nitrogen. The resulting mixture was heated to 100° C. for 8 h in microwave. The reaction mixture was cooled to room temperature, quenched with water, and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by BIOTAGE® (20-80% EtOAc/CH2Cl2, 1.5 L, then 20%-65% B/CH2Cl2, 0.9 L; B: 10% MeOH/CH2Cl2) to give 400 mg (34%) product. 1H NMR (400 MHz, CD3OD) δ ppm 9.00 (1H, s), 8.80 (1H, d, J=5.79 Hz), 8.38 (1H, d, J=1.51 Hz), 8.04 (1H, d, J=6.04 Hz), 7.96 (1H, d, J=1.51 Hz), 7.86 (1H, s), 2.73 (3H, s); LC/MS: Rt=0.98 min. LC/MS (Condition A): 245.11/247.08.

Workup

  1. temperatureThe resulting mixture was heated to 100° C. for 8 h in microwave
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with water
  4. additiondiluted with EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by BIOTAGE® (20-80% EtOAc/CH2Cl2, 1.5 L

Sources & evidence

ORD record
ord-e3c9c6e7c2b44e6cb6763f3795e458db
Source dataset
uspto-grants-2015_09
Patent number
US09145419B2

Reaction notes

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