Sulfuric Acid → [3,5-Dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

HRID 2199143Notes

Reaction equation

HRID 2199143 reaction equation
[C-:1]#[N:2].[Na+].S(=O)(=O)(O)O.[Br:9][C:10]1[CH:26]=[C:25]([CH2:27]Cl)[CH:24]=[C:23]([Br:29])[C:11]=1[CH2:12][C:13]1[CH:14]=[C:15]([CH:20]([CH3:22])[CH3:21])[C:16](=[O:19])[NH:17][N:18]=1>CS(C)=O>[Br:9][C:10]1[CH:26]=[C:25]([CH2:27][C:1]#[N:2])[CH:24]=[C:23]([Br:29])[C:11]=1[CH2:12][C:13]1[CH:14]=[C:15]([CH:20]([CH3:22])[CH3:21])[C:16](=[O:19])[NH:17][N:18]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 8929Sodium CyanideHCID 598345186-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

Product 1

HCID 59834523[3,5-Dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrileYield 67.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of sodium cyanide (279 mg, 5.69 mmol) in dimethyl sulfoxide (2.0 mL) was treated with concentrated sulfuric acid (0.10 mL), 6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one (62) (346 mg, 0.79 mmol) and an addition rinse of dimethyl sulfoxide (3.0 mL). The reaction was stirred at 25° C. for 5 min and at 40° C. for 1 h. At this time, the reaction was heated to 60° C. for 1 h and then was cooled to 25° C. The mixture was poured onto a mixture of ice and a saturated aqueous sodium bicarbonate solution (50 mL). This mixture was extracted into ethyl acetate (3×50 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1:2 hexanes/ethyl acetate) afforded [3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile (63) (227 mg, 67%) as a light orange solid; LRMS for C16H15Br2N3O (M+H) at m/z=424. Molecular Weight=425.1255; Exact Mass=422.9582

Workup

  1. additionan addition
  2. washrinse of dimethyl sulfoxide (3.0 mL)
  3. temperatureAt this time, the reaction was heated to 60° C. for 1 h
  4. temperaturewas cooled to 25° C
  5. additionThe mixture was poured onto a mixture of ice
  6. extractionThis mixture was extracted into ethyl acetate (3×50 mL)
  7. washThe combined organics were washed with a saturated aqueous sodium chloride solution (1×50 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4e04a4fefff24ee79c860f90843a4ae9
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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