3,6-Dichloropyridazine → HCID 86649248, compound

HRID 80419Notes

Reaction equation

HRID 80419 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[Cl-].C(C1C=CC=C(CCC)C=1[N+:22]1[CH:26]=[CH:25][N:24]([C:27]2[C:32]([CH2:33][CH2:34][CH3:35])=[CH:31]C=CC=2CCC)[CH:23]=1)CC.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[N:3]=[N:4][C:5]([N:22]2[CH2:35][CH:34]3[CH2:23][N:24]4[CH2:27][CH:32]([CH2:31][CH:26]2[CH2:25]4)[CH2:33]3)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 673313,6-DichloropyridazineHCID 22314747HCID 22314747, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 86649248HCID 86649248, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of the product of Example 2 (0.30 g, 2.0 mmol) in dry toluene (10 mL) was treated with 3,6-dichloropyridazine (0.71 g, 4.8 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3; 0.037 g, 0.04 mmol; Alfa Aesar), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (0.057 g, 0.12 mmol; Strem), and sodium tert-butoxide (0.45 g, 4.0 mmol; Aldrich). The mixture was purged with nitrogen and heated to 90° C. for 8 hours. After cooling to room temperature, the reaction was quenched by pouring into a 5% aqueous NaHCO3 solution. The mixture was extracted with chloroform (3×), washed with brine, dried (MgSO4), filtered and concentrated. The crude product was purified by preparative HPLC [Waters 30×100 mm XBridge Prep C18, 5 μm, 40 mL/min, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: MS (DCI/NH3) m/z 265 (M+H)+.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperatureAfter cooling to room temperature
  3. customthe reaction was quenched
  4. additionby pouring into a 5% aqueous NaHCO3 solution
  5. extractionThe mixture was extracted with chloroform (3×)
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparative HPLC [Waters 30×100 mm XBridge Prep C18, 5 μm, 40 mL/min, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-82da3ac08f8140d7b4c1f0dbabccfa47
Source dataset
uspto-grants-2014_09
Patent number
US08846661B2

Reaction notes

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