6-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carboxamide → 6-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrile

HRID 869165Notes

Reaction equation

HRID 869165 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([CH3:12])[CH3:11])=[C:4]([C:20]([NH2:22])=O)[CH:3]=1>O=P(Cl)(Cl)Cl>[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)([CH3:12])[CH3:11])=[C:4]([C:20]#[N:22])[CH:3]=1

Participants

3

Reactant 1

HCID 866861336-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carboxamide

Product 1

HCID 866861346-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrileYield 19%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

To a portion of 6-chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carboxamide (3.4 g, 11 mmol, 1.0 equiv) was added POCl3 (10 mL) at room temperature. The mixture was stirred at reflux for 3 hours and then quenched by pouring it into ice water containing NaHCO3. Dioxane and EtOAc were added to facilitate mixing of the layers. The layers were allowed to separate and the aqueous layer was extracted with EtOAc and the combined organic phases were washed with saturated NaCl. The organics were dried over Na2SO4 and evaporated to dryness in vacuo. Purification over silica gel using a gradient of 10-20% EtOAc/hexanes yielded the desired product (0.60 g, 19%) as a yellow oil.

Workup

  1. temperatureat reflux for 3 hours
  2. customquenched
  3. additionby pouring it into ice water
  4. additioncontaining NaHCO3
  5. additionDioxane and EtOAc were added
  6. additionto facilitate mixing of the layers
  7. customto separate
  8. extractionthe aqueous layer was extracted with EtOAc
  9. washthe combined organic phases were washed with saturated NaCl
  10. dry with materialThe organics were dried over Na2SO4
  11. customevaporated to dryness in vacuo
  12. customPurification over silica gel using a gradient of 10-20% EtOAc/hexanes

Sources & evidence

ORD record
ord-68a13d112d164a98aea4eb52b288d570
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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