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

HRID 2199128Notes

Reaction equation

HRID 2199128 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 75 L) 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 75 L)
  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-e3f0e18199f24aeea56dcea48a86703c
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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