Phosphorus oxychloride → 4-Chloro-1,5-naphthyridine-3-carbonitrile

HRID 276839Notes

Reaction equation

HRID 276839 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[C:12]#[N:13].O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[C:12]#[N:13]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178510307HCID 178510307, compound

Product 1

HCID 185489474-Chloro-1,5-naphthyridine-3-carbonitrileYield 28.5%

Procedure

A solution of 4-hydroxyl-[1.5]naphthyridine-3-carbonitrile (1.0 g, mmol) in 20 ml POCl3 was refluxed for 3 hrs. After cooling, the solvent was removed by rotary evaporation. The residue was treated with ice-water mixture, made basic by NH4OH, and extracted with CH2Cl2. Removal of the solvent gave 4-chloro-[1.5]naphthyridine-3-carbonitrile (285 mg, 28.5%). This was heated at reflux with 3-bromoaniline (3 eq) in the presence of pyridine HCl salt (350 mg) in ethoxyethanol for 3 hrs under argon. After cooling, the solvent was removed by rotary evaporation. The residue was partitioned between ice-water and ethyl acetate, made basic with (NH4OH), extracted with ethyl acetate. The combined extracts were washed (brine) and dried (Na2SO4), and concentrated. The residue was triturated with ether. The title compound was collected and washed with ether, and dried. mass spectrum (electrospray, m/e): 326.9 (M+H); IR cm-1: 3372, 2209; H-NMR δ(DMSO-d6): 7.36-7.90 (3H, m, C4′ C5′-H and C6′ Hs in bromoaniline), 7.64 (1H, s, C2′-H), 7.94 (1H, dd, C7-H), 8.36 (1H, dd, C8-H), 8.66 (1H, s, C2-H), 8.98 (1H, dd, C6-H), 10.47 (1H, bs, NH).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed by rotary evaporation
  3. additionThe residue was treated with ice-water mixture
  4. extractionextracted with CH2Cl2
  5. customRemoval of the solvent

Sources & evidence

ORD record
ord-edd6ad4a29e541c5beb4e39554ee0004
Source dataset
uspto-grants-2002_03
Patent number
US06355636B1

Reaction notes

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