Pyridine → 8-chloro-5-phenylpyrido[3,2-d]pyridazine
Reaction equation
[C:1]1([C:7]2[C:8]3[CH:17]=[CH:16][CH:15]=[N:14][C:9]=3[C:10](=O)[NH:11][N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.P(Cl)(Cl)([Cl:26])=O>>[Cl:26][C:10]1[C:9]2[N:14]=[CH:15][CH:16]=[CH:17][C:8]=2[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:12][N:11]=1Participants
Conditions
- Temperature
- 110 °C
Procedure
To 5-phenylpyrido[2,3-d]pyridazin-8(7H)-one (1.39 g, 6.2 mmol) and pyridine (0.50 ml, 6.2 mmol) was added phosphorus oxychloride (12 ml, 125 mmol). The slurry was heated to 110° C. for 1 hour. After cooling to room temperature, the reaction was poured into 200 mL of ice-water. The mixture was extracted with 4×50 mL of chloroform. The chloroform layer was washed with 1×50 mL H2O, 1×50 mL 1N NaOH, and 1×50 mL of H2O. The organic layer was dried over Na2SO4, filtered, and concentrated. Silica gel column chromatography afforded 8-chloro-5-phenylpyrido[3,2-d]pyridazine 71 (1.2 g). 1H-NMR (400 MHz, CDCl3): δ 9.42 (d, J=2.7 Hz, 1H), 8.45 (d, J=7.8 Hz, 1H), 7.89 (m, 1H), 7.73 (br s, 2H), 7.61 (br s, 3H). MS 241.0 (calc'd) 242.0 (M+H, found).
Workup
- temperatureAfter cooling to room temperature
- extractionThe mixture was extracted with 4×50 mL of chloroform
- washThe chloroform layer was washed with 1×50 mL H2O, 1×50 mL 1N NaOH, and 1×50 mL of H2O
- dry with materialThe organic layer was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-d5e55a0c374346ef99c4f9683cfc9d5e
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08222251B2
Reaction notes
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