Diisopropylethylamine → 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

HRID 1890960Notes

Reaction equation

HRID 1890960 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][CH:11]=3)[CH:4]=[N:3]1.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.[CH3:76][C:77]1[CH:78]=[CH:79][C:80]2[N:81]([C:83]([SH:86])=[N:84][N:85]=2)[N:82]=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]>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([S:86][C:83]2[N:81]4[N:82]=[C:77]([CH3:76])[CH:78]=[CH:79][C:80]4=[N:85][N:84]=2)=[CH:12][CH:11]=3)[CH:4]=[N:3]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57742328trifluoro-methanesulfonic acid 3-(1-methyl-1H-pyrazol-4-yl)-quinolin-6-yl esterHCID 178423528HCID 178423528, compound

Product 1

HCID 249009753-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinolineYield 79.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of trifluoro-methanesulfonic acid 3-(1-methyl-1H-pyrazol-4-yl)-quinolin-6-yl ester (15.9 g, 44.79 mmol), diisopropylethylamine (15.5 mL, 89.58 mmol) in DMF (150 mL) under nitrogen was degassed by bubbling with nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium (2.0 g, 2.24 mmol, Strem catalyst) and Xantphos (2.54 g, 4.48 mmol) were added together in one portion, followed by 6-methyl-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (7.44 g, 44.79 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 4 h. The reaction mixture was filtered while hot and the filtrate was cooled to precipitate. The solid was collected and washed with methanol to give an off-white solid, which was purified via column chromatography to get 13.3 g of 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (79% yield).

Workup

  1. customby bubbling with nitrogen for 30 min
  2. filtrationThe reaction mixture was filtered while hot and the filtrate
  3. temperaturewas cooled
  4. customto precipitate
  5. customThe solid was collected
  6. washwashed with methanol
  7. customto give an off-white solid, which
  8. customwas purified via column chromatography

Sources & evidence

ORD record
ord-b488d63816be4f24a2f37fbd922df89d
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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