Phosphorus oxychloride → 8-Chloro-5-fluoro-1,7-naphthyridine-3-carbonitrile

HRID 930467Notes

Reaction equation

HRID 930467 reaction equation
[F:1][CH:2]1[CH:11](OC)[NH:10][C:9](=O)[C:8]2[N:7]=[CH:6][C:5]([C:15]#[N:16])=[CH:4][C:3]1=2.P(Cl)(Cl)([Cl:19])=O>C(#N)C>[Cl:19][C:9]1[N:10]=[CH:11][C:2]([F:1])=[C:3]2[C:8]=1[N:7]=[CH:6][C:5]([C:15]#[N:16])=[CH:4]2

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 867281405-Fluoro-6-methoxy-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 867158748-Chloro-5-fluoro-1,7-naphthyridine-3-carbonitrileYield 56.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A pressure bottle was charged with 5-fluoro-6-methoxy-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carbonitrile (step 3, 2.27 g, 10.26 mmol), acetonitrile (41 ml) and phosphorus oxychloride (Aldrich, 3.35 ml, 35.9 mmol). The bottle was sealed and the reaction mixture was heated to 75° C. overnight. The reaction mixture was concentrated and the crude material was purified by silica gel chromatography (gradient 0-20% (10 MeOH in DCM)/DCM to afford the title compound (1.2 g, 5.78 mmol, 56.3% yield) as a white solid. MS m/z=208 [M+H]+. Calculated for C9H3ClFN3: 207.0

Workup

  1. customThe bottle was sealed
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude material was purified by silica gel chromatography (gradient 0-20% (10 MeOH in DCM)/DCM

Sources & evidence

ORD record
ord-fed7a6be780045159055c873aad6cc50
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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