3,6-Dichloro-4-isopropylpyridazine → (4-Amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

HRID 271181Notes

Reaction equation

HRID 271181 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[CH:8]([CH3:10])[CH3:9].[NH2:12][C:13]1[CH:18]=[C:17]([Cl:19])[C:16]([CH2:20][C:21]#[N:22])=[C:15]([Cl:23])[CH:14]=1.CC(C)([O-])C.[K+]>O1CCCC1.C(OCC)(=O)C>[NH2:12][C:13]1[CH:14]=[C:15]([Cl:23])[C:16]([CH:20]([C:5]2[N:4]=[N:3][C:2]([Cl:1])=[C:7]([CH:8]([CH3:10])[CH3:9])[CH:6]=2)[C:21]#[N:22])=[C:17]([Cl:19])[CH:18]=1

Participants

6

Reactant 3

HCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 23665647Potassium tert-butoxideHCID 59834534(4-Amino-2,6-dichloro-phenyl)-acetonitrile

Product 1

HCID 59834538(4-Amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrileYield 77%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 3,6-dichloro-4-isopropyl pyridazine (7) (5.54 g, 29.0 mmol) in tetrahydrofuran (116 mL) in a 500 mL round bottom flask (caution: use an extra large flask) was treated with (4-amino-2,6-dichloro-phenyl)-acetonitrile (44) (5.81 g, 28.9 mmol). The reaction mixture was equipped with a cold water condenser and heated to 60° C. The flask was then raised out of the oil bath and potassium tert-butoxide (6.85 g, 57.99 mmol) was added. The mixture was heated to 60° C. for 45 min. The reaction was cooled to room temperature, transferred to a separatory funnel, diluted with ethyl acetate (500 mL) and was washed with a saturated aqueous sodium chloride solution (2×250 mL). The organic layer was separated, dried with magnesium sulfate, and was filtered. Silica gel 60 (70-230 mesh) was added to the filtrate and the solvent was concentrated under vacuum. The resulting mixture was purified by flash chromatography (Biotage 75L) using silica gel eluted with 15%-30% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford (4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile (45) (7.87 g, 77%) as an orange foam; LRMS for C15H13Cl3N4 (M+H) m/z=355. This compound was used without further purification. Molecular Weight=355.6567; Exact Mass=354.0206

Workup

  1. customThe reaction mixture was equipped with a cold water condenser
  2. additionwas added
  3. temperatureThe mixture was heated to 60° C. for 45 min
  4. temperatureThe reaction was cooled to room temperature
  5. customtransferred to a separatory funnel
  6. washwas washed with a saturated aqueous sodium chloride solution (2×250 mL)
  7. customThe organic layer was separated
  8. dry with materialdried with magnesium sulfate
  9. filtrationwas filtered
  10. additionSilica gel 60 (70-230 mesh) was added to the filtrate
  11. concentrationthe solvent was concentrated under vacuum
  12. customThe resulting mixture was purified by flash chromatography (Biotage 75L)
  13. washeluted with 15%-30% ethyl acetate in hexanes
  14. customThe desired fractions were collected
  15. concentrationconcentrated under vacuum
  16. customto afford a solid which
  17. customwas dried under high vacuum

Sources & evidence

ORD record
ord-edc4f8e663f94b8ebc3f40b654a50218
Source dataset
uspto-grants-2008_11
Patent number
US07452882B2

Reaction notes

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