Sodium Hydroxide → 7-methyl-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline

HRID 1890948Notes

Reaction equation

HRID 1890948 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1OS(C(F)(F)F)(=O)=O.C(N(C(C)C)CC)(C)C.[CH3:29][N:30]1[CH:34]=[C:33]([C:35]2[CH:36]=[CH:37][C:38]3[N:39]([C:41]([SH:44])=[N:42][N:43]=3)[N:40]=2)[CH:32]=[N:31]1.[OH-].[Na+]>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].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>[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[S:44][C:41]1[N:39]2[N:40]=[C:35]([C:33]3[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=3)[CH:36]=[CH:37][C:38]2=[N:43][N:42]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 57911006Trifluoromethanesulfonic acid 7-methyl-quinolin-6-yl esterHCID 178480034HCID 178480034, compound

Product 1

HCID 249007307-methyl-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinolineYield 62%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of trifluoromethanesulfonic acid 7-methyl-quinolin-6-yl ester (1.38 g, 4.74 mmol), diisopropylethylamine (1.5 mL, 8.61 mmol) in DMF (8 mL) under nitrogen was degassed by bubbling in nitrogen for 20 min. Tris(dibenzylideneacetone)dipalladium (99 mg, 0.11 mmol, Strem catalyst) and Xantphos (125 mg, 0.215 mmol) were added together in one portion, followed by 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (1 g, 4.36 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and poured onto 2 M aqueous NaOH (100 mL). The resulting precipitate was filtered, washed with water, and air-dried for 30 min. The resulting cake was dissolved in MeOH (80 mL) and CHCl3 (80 mL), and 2 g of activated decolorizing charcoal were added. The suspension was stirred at 60° C. for 2.5 h. Celite (10 g) was then added and the warm mixture was filtered over a short silica gel plug. The filtrate was evaporated in vacuo to give a beige solid. Recrystallization from EtOH and chloroform afforded 1.0 g of 7-methyl-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline as white crystals (62% yield).

Workup

  1. customby bubbling in nitrogen for 20 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationThe resulting precipitate was filtered
  4. washwashed with water
  5. customair-dried for 30 min
  6. dissolutionThe resulting cake was dissolved in MeOH (80 mL)
  7. additionCHCl3 (80 mL), and 2 g of activated decolorizing charcoal were added
  8. stirringThe suspension was stirred at 60° C. for 2.5 h
  9. additionCelite (10 g) was then added
  10. filtrationthe warm mixture was filtered over a short silica gel plug
  11. customThe filtrate was evaporated in vacuo
  12. customto give a beige solid
  13. customRecrystallization from EtOH and chloroform

Sources & evidence

ORD record
ord-a3962cb39f72461b842e7951790d6a0e
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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