Toluene → 1-Benzyloxymethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097498Notes

Reaction equation

HRID 2097498 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[N:16][NH:17][C:18](=[O:19])[C:13]=2[CH:12]=[C:11]1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C(N(CC)C(C)C)(C)C.[H][H]>[Pd].O1CCCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[N:16][NH:17][C:18](=[O:19])[C:13]=2[CH:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 81531DiisopropylethylamineHCID 666023361-Benzyloxymethyl-2-bromo-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 666027621-Benzyloxymethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 95.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 33.4 g (100 mmol) of 1-benzyloxymethyl-2-bromo-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 17-(d) were added 4.5 g of 5% palladium-active carbon, 330 ml of toluene, 330 ml of tetrahydrofuran and 21 ml (121 mmol) of N,N-diisopropylethylamine, and the mixture was stirred under 1 atm hydrogen atmosphere at 60° C. for 1 hour. After completion of the reaction, the insoluble material in the reaction suspension was removed by filtration, followed by washing with 300 ml of a mixed solution (chloroform/methanol=1/1 (V/V)), and the filtrate and the washing solution were combined, then concentrated under reduced pressure. To the obtained concentrate was added 400 ml of water, and the mixture was extracted with a mixed solvent comprising 500 ml of chloroform and 30 ml of ethanol. The organic layer after separation was washed successively with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 24.3 g of the title compound as a yellowish brown solid. (Yield: 95%)

Workup

  1. customAfter completion of the reaction
  2. customthe insoluble material in the reaction suspension was removed by filtration
  3. washby washing with 300 ml of a mixed solution (chloroform/methanol=1/1 (V/V))
  4. concentrationconcentrated under reduced pressure
  5. concentrationTo the obtained concentrate
  6. additionwas added 400 ml of water
  7. extractionthe mixture was extracted with a mixed solvent
  8. customThe organic layer after separation
  9. washwas washed successively with water
  10. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e87659b7d40f448dba9e67ce771dc63b
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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