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

HRID 627682Notes

Reaction equation

HRID 627682 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.O=P(Cl)(Cl)[Cl:19]>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 (2.27 g, 10.26 mmol), acetonitrile (41.1 ml) and POCl3 (3.35 ml, 35.9 mmol). The bottle was sealed and the reaction was heated at 75° C. for 17 h. Upon cooling to RT the mixture was concentrated and the crude material was purified by silica gel chromatography, using a gradient of 0-20% 90/10 DCM/MeOH in DCM. 8-chloro-5-fluoro-1,7-naphthyridine-3-carbonitrile (1.2 g, 5.78 mmol, 56.3% yield) was isolated as a white solid. LC/MS (ESI+) m/z=208.0 (M+H).

Workup

  1. customThe bottle was sealed
  2. temperatureUpon cooling to RT the mixture
  3. concentrationwas concentrated
  4. customthe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ed68d95e6bd14fbeb1275b36a7d5e664
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…