Diisopropylethylamine → 2-Chloro-6-(3,3-difluoroazetidin-1-yl)-4-iodopyridine
Reaction equation
Cl[C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.Cl.[F:11][C:12]1([F:16])[CH2:15][NH:14][CH2:13]1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(OCC)(=O)C>[Cl:9][C:4]1[CH:5]=[C:6]([I:8])[CH:7]=[C:2]([N:14]2[CH2:15][C:12]([F:16])([F:11])[CH2:13]2)[N:3]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
To a suspension of 2,6-dichloro-4-iodopyridine (1 g, 3.65 mmol) and 3,3-difluoroazetidine hydrochloric acid salt (0.497 g, 3.83 mmol) in 25 mL tetrahydrofuran was added diisopropylethylamine (0.797 ml, 4.56 mmol). The reaction mixture was heated at 90° C. for 16 hours. Further addition of another equivalent of amine and base was performed, and the suspension was heated at 100° C. for several hours, and then cooled, diluted with ethyl acetate, washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue was purified on silica gel using flash chromatography (5% to 20% ethyl acetate/hexane) to afford 0.6 g of the title compound. MS (DCI+) m/z 331.0 (M+H)+.
Workup
- temperaturethe suspension was heated at 100° C. for several hours
- temperaturecooled
- washwashed with water, brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified on silica gel using flash chromatography (5% to 20% ethyl acetate/hexane)
Sources & evidence
- ORD record
- ord-04b73413fc8f47f59614d0371babcbdc
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08435980B2
Reaction notes
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