6-Amino-3-chloropyridazine → Imidazo(1,2-b)pyridazine, 6-chloro-
Reaction equation
C(OC(O[CH2:8][CH3:9])CBr)C.C(=O)(O)[O-].[Na+].[Cl:15][C:16]1[N:21]=[N:20][C:19]([NH2:22])=[CH:18][CH:17]=1>C(O)C>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]2[N:20]([CH:8]=[CH:9][N:22]=2)[N:21]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
Bromoacetaldehyde diethylacetal (36.5 g, 216 mmol) was added to a solution of aq.cHBr (7.2 ml) and then heated to reflux for 30 min. The mixture was then cooled to 0° C., upon which ethanol (236 ml), sodium bicarbonate (8.09 g, 95 mmol) and 6-chloropyridazin-3-amine (4 g, 30 mmol) were added. The mixture was heated to 80° C. for 3 h (reaction was monitored by TLC) and then allowed to cool to RT. The mixture was concentrated under reduced pressure, diluted with water and extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 15% ethyl acetate in n-hexane and silica gel (230-400 mesh), to afford 6-chloroimidazo[1,2-b]pyridazine (4.0 g, 85.2%) as Off-white solid. 1H NMR: 200 MHz, CDCl3: δ 7.4-7.2 (Ar, 4H), 3.85 (q, 1H), 3.4 (q, 1H), 3.2 (q, 2H), 1.35 (t, 3H), 1.1 (t, 3H). MS: [M+H]+: m/z=154.3.
Workup
- temperatureheated
- temperatureto reflux for 30 min
- additionwere added
- custom(reaction was monitored by TLC)
- temperatureto cool to RT
- concentrationThe mixture was concentrated under reduced pressure
- additiondiluted with water
- extractionextracted with EtOAc
- dry with materialThe combined organics were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by flash column chromatography
Sources & evidence
- ORD record
- ord-6ea09cfa35264745a39315fbcfa762a6
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08343973B2
Reaction notes
Loading…