Methane → 6-{6-[1-(2-Trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl}-quinoline

HRID 1890952Notes

Reaction equation

HRID 1890952 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2)(=O)=O.C(N(C(C)C)CC)(C)C.[CH3:28][Si:29]([CH3:50])([CH3:49])[CH2:30][CH2:31][O:32][CH2:33][N:34]1[CH:38]=[C:37]([C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:45]([SH:48])=[N:46][N:47]=3)[N:44]=2)[CH:36]=[N:35]1.C>CN(C=O)C>[CH3:28][Si:29]([CH3:50])([CH3:49])[CH2:30][CH2:31][O:32][CH2:33][N:34]1[CH:38]=[C:37]([C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:45]([S:48][C:7]4[CH:8]=[C:9]5[C:14](=[CH:15][CH:16]=4)[N:13]=[CH:12][CH:11]=[CH:10]5)=[N:46][N:47]=3)[N:44]=2)[CH:36]=[N:35]1

Participants

6

Reactant 4

HCID 297MethaneHCID 81531DiisopropylethylamineHCID 152903586-Quinolinyl trifluoromethanesulfonateHCID 178504226HCID 178504226, compound

Product 1

HCID 689770066-{6-[1-(2-Trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl}-quinolineYield 37.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 6-quinolinyl trifluoromethanesulfonate (436 mg, 1.57 mmol), diisopropylethylamine (0.746 mL, 4.29 mmol) in DMF (3.8 mL) under nitrogen was degassed by bubbling in nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium (33 mg, 2.5 mol %, Strem catalyst) and Xantphos (41 mg, 5 mol %) were added together in one portion, followed by 6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (498 mg, 1.43 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 3 h before 500 mg of activated decolorizing charcoal were added. The suspension was stirred at 70° C. for 20, then the warm mixture was directly filtered through a plug of celite, using DMF as eluent. The solvent was evaporated in vacuo and the residue taken up in dichloromethane and washed with 1N aqueous NaOH and concentrated onto silica gel and purified by flash column chromatography eluting with dichloromethane:methanol 100:0 to 92:8 to return title compound as a light yellow foam (250 mg, 0.53 mmol, 37% yield): 1H NMR (DMSO-d6) δ 0.00 (9H, s), 0.90 (2H, t), 3.62 (2H, t), 5.54 (2H, s), 7.62 (1H, dd), 7.83 (1H, dd), 7.91 (1H, d), 8.07 (1H, d), 8.18 (1H, s), 8.23 (1H, d), 8.43 (1H, dd), 8.57 (1H, d), 8.75 (1H, d), 8.96 (1H, dd); MS (m/z) 476 [M+H]+.

Workup

  1. customby bubbling in nitrogen for 30 min
  2. additionTris(dibenzylideneacetone)dipalladium (33 mg, 2.5 mol %, Strem catalyst) and Xantphos (41 mg, 5 mol %) were added together in one portion
  3. additionwere added
  4. filtrationthe warm mixture was directly filtered through a plug of celite
  5. customThe solvent was evaporated in vacuo
  6. washwashed with 1N aqueous NaOH
  7. concentrationconcentrated onto silica gel
  8. custompurified by flash column chromatography
  9. washeluting with dichloromethane:methanol 100:0 to 92:8

Sources & evidence

ORD record
ord-d28a9ed27f744325b82326c6fda32a61
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

Loading…