Phosphorus oxychloride → 6-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carbonitrile

HRID 877664Notes

Reaction equation

HRID 877664 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](O)=[C:8]([C:11]#[N:12])[CH:7]=[N:6][N:5]2[CH:13]=1.O=P(Cl)(Cl)[Cl:16]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([Cl:16])=[C:8]([C:11]#[N:12])[CH:7]=[N:6][N:5]2[CH:13]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178510449HCID 178510449, compound

Product 1

HCID 682911366-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carbonitrileYield 47.7%

Conditions

Temperature
75 °C

Procedure

To a 25 mL round bottom flask was added 6-bromo-4-hydroxypyrrolo[1,2-b]pyridazine-3-carbonitrile (16.5 g, 69.47 mmol) and POCl3 (85 mL, 0.88 mol) and the reaction mixture was stirred and heated at 75° C. for 3 hours. The POCl3 was removed under vacuum and the resulting residue was dissolved in CH2Cl2. The solution was cooled to 0° C. and saturated aq. NaHCO3 solution was added and the biphasic mixture was stirred vigorously while allowing to warm to rt. The organic layer was separated and concentrated and the obtained residue was purified by flash silica gel column chromatography to yield 8.5 g (29%) of the title compound as a yellow solid. HPLC (condition P): retention time=16.74 min. H1 NMR (400 MHz, CDCl3) δ ppm: 8.09 (1H, s), 7.94 (1H, d, 2.0 Hz), 7.06 (1H, d, 2.0 Hz).

Workup

  1. customThe POCl3 was removed under vacuum
  2. dissolutionthe resulting residue was dissolved in CH2Cl2
  3. temperatureThe solution was cooled to 0° C.
  4. additionsaturated aq. NaHCO3 solution was added
  5. stirringthe biphasic mixture was stirred vigorously
  6. temperatureto warm to rt
  7. customThe organic layer was separated
  8. concentrationconcentrated
  9. customthe obtained residue was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-fc1127327c534886a8293e75b0e966ec
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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