6-Bromoquinoline → Sgx-523

HRID 1890946Notes

Reaction equation

HRID 1890946 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.C(N(C(C)C)CC)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:63][N:64]1[CH:68]=[C:67]([C:69]2[CH:70]=[CH:71][C:72]3[N:73]([C:75]([SH:78])=[N:76][N:77]=3)[N:74]=2)[CH:66]=[N:65]1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:63][N:64]1[CH:68]=[C:67]([C:69]2[CH:70]=[CH:71][C:72]3[N:73]([C:75]([S:78][C:2]4[CH:3]=[C:4]5[C:9](=[CH:10][CH:11]=4)[N:8]=[CH:7][CH:6]=[CH:5]5)=[N:76][N:77]=3)[N:74]=2)[CH:66]=[N:65]1

Participants

7

Reactant 4

HCID 792436-BromoquinolineHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 178480034HCID 178480034, compound

Product 1

HCID 24779724Sgx-523Yield 58.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 6-bromoquinoline (45 mg, 0.215 mmol), diisopropylethylamine (0.075 mL, 0.43 mmol) in DMF (1 mL) under nitrogen was degassed by bubbling in nitrogen for 5 min. Tris(dibenzylideneacetone)dipalladium (11 mg, 0.011 mmol), Xantphos (13 mg, 0.022 mmol), and 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (50 mg, 0.215 mmol) were added, and the mixture was degassed for another 5 min. The reaction mixture was stirred at 100° C. for 23 h. More palladium catalyst (11 mg) and ligand (13 mg) were added after 6 h. The reaction mixture was cooled to room temperature, filtered through a 0.45 um filter, and the crude mixture was purified directly by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier) to provide 45 mg of 6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline as a yellow solid (58% yield).

Workup

  1. customby bubbling in nitrogen for 5 min
  2. customthe mixture was degassed for another 5 min
  3. additionMore palladium catalyst (11 mg) and ligand (13 mg) were added after 6 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered through a 0.45 um
  6. filtrationfilter
  7. customthe crude mixture was purified directly by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier)

Sources & evidence

ORD record
ord-3efc9dab0cfe4c5f96a6a93a7f8b98c1
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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