Sulfuric Acid → HCID 57929919, compound

HRID 1930041Notes

Reaction equation

HRID 1930041 reaction equation
[C:1]([C:5]1[N:9]2[N:10]=[C:11]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])[CH:12]=[CH:13][C:8]2=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:24]S(O)(=O)=O.[OH-].[Na+]>>[C:1]([C:5]1[N:9]2[N:10]=[C:11]([CH2:14][C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])=[O:24])[CH:12]=[CH:13][C:8]2=[N:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 57929850HCID 57929850, compound

Product 1

HCID 57929919HCID 57929919, compound

Conditions

Temperature
90 °C

Procedure

To a round bottom flask was added 3-tert-butyl-6-((2,4-difluorophenyl)ethynyl)-[1,2,4]triazolo[4,3-b]pyridazine (0.60 g, 1.92 mmol) and 60% aqueous H2SO4 (8.53 mL, 96 mmol). The reaction mixture was heated to about 90° C. for about 2 h. The reaction mixture was diluted with ice water (10 mL) and it was basified with 50% aqueous NaOH to a pH of about 9. The product was dried over MgSO4, filtered, and concentrated in vacuo to afford 2-(3-tert-butyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1-(2,4-difluorophenyl)ethanone which was carried forward without additional purification. To a mixture of 2-(3-tert-butyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1-(2,4-difluorophenyl)ethanone in toluene (3 mL) was added 1,1-dimethoxy-N,N-dimethylethanamine (0.21 g, 1.73 mmol). The mixture was heated to about 100° C. for about 30 min. The toluene was removed in vacuo and the material was redissolved in 1,4-dioxane (3 mL). Anhydrous hydrazine (0.085 mL, 1.7 mmol) was added dropwise to the solution and it was heated to about 95° C. for about 30 min. The mixture was cooled to ambient temperature and the material was concentrated in vacuo. The material was purified by flash chromatography and eluted with DCM/MeOH (gradient, 1-4% MeOH) to afford the title compound (0.31 g, 46%): LC/MS (Table 1, Method a) Rt=1.82 min; MS m/z: 355.2 (M+H)+; 1H NMR (DMSO-d6) δ 1.17 (s, 9H), 7.19 (m, 1H), 7.32 (m, 1H), 7.56 (m, 1H), 7.63 (d, 1H), 8.28 (d, 1H), 8.66 (s (br), 1H), 13.66 (s (br), 1H).

Workup

  1. dry with materialThe product was dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-75a6eed267b74be19fd19012a22fce68
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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