Piperidine → 2-(3-Fluorophenyl)-1,5-naphthyridine-3-carbonitrile
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH2:9][C:10]#[N:11])[CH:5]=[CH:6][CH:7]=1.[NH2:13][C:14]1[C:15]([CH:20]=O)=[N:16][CH:17]=[CH:18][CH:19]=1.C(OCC)(=O)C.N1CCCCC1>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([C:10]#[N:11])=[CH:20][C:15]3[C:14](=[CH:19][CH:18]=[CH:17][N:16]=3)[N:13]=2)[CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 85 °C
Procedure
To a mixture of 3-(3-fluorophenyl)-3-oxopropanenitrile (0.8991 g, 5.511 mmol) and 3-amino-2-pyridinecarbaldehyde (0.6730 g, 5.511 mmol) in ethyl acetate (16.70 mL, 5.511 mmol) was added piperidine (0.04360 mL, 0.4409 mmol) and the mixture was heated under reflux (bath temp. 85° C.) with stirring. After 1 h, the mixture was cooled to room temperature and concentrated under reduced pressure to give a dark brown solid. The dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 2-(3-fluorophenyl)-1,5-naphthyridine-3-carbonitrile as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.27 (1H, d, J=0.8 Hz), 9.18 (1H, dd, J=4.1, 1.8 Hz), 8.56-8.62 (1H, m), 8.01 (1H, dd, J=8.6, 3.9 Hz), 7.76-7.85 (2H, m), 7.63-7.71 (1H, m), 7.44-7.52 (1H, m); LC-MS (ESI) m/z 249.9 [M+H]+.
Workup
- temperaturethe mixture was heated
- temperaturethe mixture was cooled to room temperature
- concentrationconcentrated under reduced pressure
- customto give a dark brown solid
- customThe dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
- customover 25 min
Sources & evidence
- ORD record
- ord-913b5cf6918c4071bf9617b1c257bee9
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08633313B2
Reaction notes
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