Sulfuric Acid → 6-(1-tert-Butyl-3-(2,4-difluorophenyl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1930055Notes

Reaction equation

HRID 1930055 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][NH:11][N:10]=1.S(=O)(=O)(O)O>CC(O)(C)C>[C:3]([N:11]1[CH:12]=[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)[C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[N:10]1)([CH3:9])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 178440301HCID 178440301, compound

Product 1

HCID 579299646-(1-tert-Butyl-3-(2,4-difluorophenyl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazineYield 47.5%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

The 6-(3-(2,4-Difluorophenyl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.300 g, 0.881 mmol, Example #L.1.1) was suspended in t-BuOH (3.0 mL) then sulfuric acid (0.15 g, 1.5 mmol) was added. The mixture was heated using a CEM® microwave at about 130° C. for about 10 min (250 psi maximum pressure, 10 min ramp, 300 max watts). The reaction mixture was concentrated under reduced pressure then purified by flash chromatography on silica gel using 9:1 DCM/MeOH as an eluent to give the title compound (0.083 g, 24%): LC/MS (Table 1, Method a) Rt=2.90 min; MS m/z: 397.3 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. customat about 130° C.
  3. customfor about 10 min
  4. custom(250 psi maximum pressure, 10 min ramp, 300 max watts)
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. customthen purified by flash chromatography on silica gel using 9:1 DCM/MeOH as an eluent

Sources & evidence

ORD record
ord-25d5428ec0844b88b6fd0d794d4a25d6
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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