Phosphorus oxychloride → 3,8-Dichloro-5-fluoro-1,7-naphthyridine
Reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=O)[NH:7][CH:8](OC)[CH:9]([F:12])[C:10]=2[CH:11]=1.P(Cl)(Cl)([Cl:18])=O>C(#N)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[C:9]([F:12])[CH:8]=[N:7][C:6]=2[Cl:18]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
A vial was charged with 3-chloro-5-fluoro-6-methoxy-6,7-dihydro-1,7-naphthyridin-8(5H)-one (7.5 g, 32.5 mmol), acetonitrile (130 mL) and phosphorus oxychloride (9.09 mL, 98 mmol), and the mixture was stirred at 75° C. for 15 hours. The mixture was concentrated, and the crude material was purified by silica gel chromatography, eluting with 0-50% ethyl acetate in heptanes, to provide the title compound (5.57 g, 25.7 mmol, 79% yield) as a white solid. LC/MS (ESI+) m/z=217 (M+H).
Workup
- concentrationThe mixture was concentrated
- customthe crude material was purified by silica gel chromatography
- washeluting with 0-50% ethyl acetate in heptanes
Sources & evidence
- ORD record
- ord-2896fb6781b245b4bb051602b8489293
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296734B2
Reaction notes
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