Potassium Phosphate, Tribasic → HCID 86676945, compound

HRID 2284372Notes

Reaction equation

HRID 2284372 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.[CH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](B(O)O)=[CH:14][N:13]=1.[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:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:12]=[N:13][CH:14]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 3761204Isoquinoline-4-boronic acidHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 1

HCID 86676945HCID 86676945, compoundYield 55.5%

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 (0.8 g, 3.44 mmol), isoquinolin-4-ylboronic acid (0.6 g, 1.734 mmol), dioxane (16 mL), tetrakis(triphenylphosphine)palladium(0) (0.100 g, 0.087 mmol), and K3PO4 (2.60 mL, 5.20 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 4 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® (30-100% EtOAc/EtOAc/CH2Cl2, 1.2 L, then 50-100% B/EtOAc/CH2Cl2, B: 10% MeOH/EtOAc/CH2Cl2, 800 mL) to give the product (0.27 g, 55%). 1H NMR (400 MHz, CDCl3) δ ppm 9.41 (1H, s), 8.72 (1H, s), 8.66 (1H, d, J=4.53 Hz), 8.03-8.17 (1H, m), 7.90 (1H, s), 7.71 (3H, d, J=3.02 Hz), 7.26 (1H, d, J=4.53 Hz); LC/MS: Rt=1.35 min. LC/MS (Condition A): 281.13/283.13.

Workup

  1. temperatureThe resulting mixture was heated to 100° C. for 4 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® (30-100% EtOAc/EtOAc/CH2Cl2, 1.2 L

Sources & evidence

ORD record
ord-19a4ea242c9f4b53a9818a702121fa42
Source dataset
uspto-grants-2015_09
Patent number
US09145419B2

Reaction notes

Loading…