Phosphorus oxychloride → 1-Benzyl-4-chloro-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile
Reaction equation
C1([NH:7][C:8]([C:10]2[C:11](=[O:28])[N:12]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:13]3[C:18]([C:19]=2O)=[CH:17][CH:16]=[CH:15][N:14]=3)=O)CCCCC1.O=P(Cl)(Cl)[Cl:31]>>[CH2:21]([N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][N:14]=2)[C:19]([Cl:31])=[C:10]([C:8]#[N:7])[C:11]1=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1Participants
Procedure
A solution of 1-benzyl-4-hydroxy-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid cyclohexylamide (7) (1.3 g, 3.44 mmol) in neat POCl3 was heated overnight at 90° C. The solution was cooled and the excess POCl3 was distilled under vacuum. The residue was suspended in water, basified by saturated NaHCO3 solution and extracted by dichloromethane. The combined organic phase washed subsequently by a saturated NaHCO3 solution, water and brine, dried over Na2SO4, and evaporated. The residue was crystallized by acetone to yield 530 mg (52%) of 1-benzyl-4-chloro-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile (8) as white solids. MP: 188° C.; 1H-NMR (DMSO-d6): δ 5.61 (s, 2H), 7.21-7.31 (m, 5H), 7.56 (dd, J=4.8, 8.0 Hz, 1H), 8.53 (dd, J=1.6, 8.0 Hz, 1H), 8.86 (dd, J=1.6, 8.0 Hz, 1H); EIMS: 296 (M+1).
Workup
- temperatureThe solution was cooled
- distillationthe excess POCl3 was distilled under vacuum
- extractionextracted by dichloromethane
- washThe combined organic phase washed subsequently by a saturated NaHCO3 solution, water and brine
- dry with materialdried over Na2SO4
- customevaporated
- customThe residue was crystallized by acetone
Sources & evidence
- ORD record
- ord-fcbd1119d09c4b9d91b9ed443cd4f2ac
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361760B2
Reaction notes
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