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