Water → 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo-[4,3-b]pyridazine

HRID 633507Notes

Reaction equation

HRID 633507 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.[OH-].[Na+].[Cl:18][C:19]1[N:23]2[N:24]=[C:25](Cl)[CH:26]=[CH:27][C:22]2=[N:21][N:20]=1.O>COCCOC>[Cl:18][C:19]1[N:23]2[N:24]=[C:25]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[CH:26]=[CH:27][C:22]2=[N:21][N:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 14823463,6-Dichloro[1,2,4]triazolo[4,3-b]pyridazineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 675251543-chloro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo-[4,3-b]pyridazineYield 32.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
65 °C

Procedure

0.61 g of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5.3 cm3 of a 1N aqueous solution of sodium hydroxide are added to a mixture of 0.5 g of commercial 3,6-dichloro-1,2,4-triazolo[4,3-b]pyridazine in 15 cm3 of 1,2-dimethoxyethane. The reaction mixture is stirred at a temperature in the region of 20° C. for 30 minutes before the addition of 92 mg of palladium dichlorobis(triphenylphosphine). The reaction mixture is then stirred at 65° C. for 30 minutes, and then brought back to a temperature in the region of 20° C. and poured into 20 cm3 of water. The mixture obtained is extracted with 3×100 cm3 of dichloromethane and the combined organic phases are washed with 2×100 cm3 of a saturated aqueous solution of sodium chloride. The resulting organic phase is dried over sodium sulphate, filtered and concentrated by evaporation under reduced pressure. The yellow powder thus obtained is purified by chromatography on silica gel (eluent: 98/2 CH2Cl2/MeOH). 0.2 g of 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo-[4,3-b]pyridazine is thus obtained in the form of a beige powder, the characteristics of which are as follows:

Workup

  1. custombrought back to a temperature in the region of 20° C.
  2. customThe mixture obtained
  3. extractionis extracted with 3×100 cm3 of dichloromethane
  4. washthe combined organic phases are washed with 2×100 cm3 of a saturated aqueous solution of sodium chloride
  5. dry with materialThe resulting organic phase is dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customThe yellow powder thus obtained
  9. customis purified by chromatography on silica gel (eluent: 98/2 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-0f595f5ee61048d19a6a9101504f2e76
Source dataset
uspto-grants-2016_04
Patent number
US09321777B2

Reaction notes

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