Phosphorus oxychloride → 3-Chloro-5-(4-chlorophenyl)-4-(pyridin-4-yl)pyridazine

HRID 2224239Notes

Reaction equation

HRID 2224239 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][NH:11][C:10](=O)[C:9]=2[C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:23].C([O-])(O)=O.[Na+]>O>[Cl:23][C:10]1[N:11]=[N:12][CH:13]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 597167155-(4-chlorophenyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one

Product 1

HCID 597168553-Chloro-5-(4-chlorophenyl)-4-(pyridin-4-yl)pyridazineYield 94%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-(4-chlorophenyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one (5.1 g, 18.0 mmol) and POCl3 (20 mL) was stirred at 80° C. for 2 h. The reaction mixture was cooled to RT and the POCl3 was removed by rotary evaporator to obtain a gum. This gum was cooled in an ice bath and water (50 mL) was added. The pH of this mixture was adjusted to 6 with aqueous NaHCO3. The resulting mixture was extracted with EtOAc (2×75 mL). The combined organic layers were washed with water (2×50 mL) followed by saturated aqueous NaCl (2×25 mL). The organic layer was dried over MgSO4 and filtered through a silica gel pad (˜20 g). Upon evaporation of the solvents under reduced pressure, the title compound, 3-chloro-5-(4-chlorophenyl)-4-(pyridin-4-yl)pyridazine, (5.1 g, 94%) was obtained as a white solid. HPLC: 2.01 min; MS, M+H=302. 1H NMR (CDCl3, 500 MHz): δ 9.08 (1H, s), 8.56 (2H, d, J=5.0 Hz), 7.21 (2H, d, J=10.0 Hz), 7.09 (2H, d, J=5.0 Hz), 7.01 (2H, J=10.0 Hz).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customthe POCl3 was removed by rotary evaporator
  3. customto obtain a gum
  4. temperatureThis gum was cooled in an ice bath
  5. extractionThe resulting mixture was extracted with EtOAc (2×75 mL)
  6. washThe combined organic layers were washed with water (2×50 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered through a silica gel pad (˜20 g)
  9. customUpon evaporation of the solvents under reduced pressure

Sources & evidence

ORD record
ord-fcd17437a891432398bc3a3802940f27
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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