Sodium Iodide → 1-(4,6-Dihydroxy-1,5-naphthyridin-3-yl)ethanone

HRID 2178877Notes

Reaction equation

HRID 2178877 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][CH:10]=[C:11]([C:17](=[O:19])[CH3:18])[C:12]([O:14]CC)=O)=[CH:5][CH:4]=1.C[Si](Cl)(C)C.[I-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[OH:14][C:12]1[C:7]2[C:6](=[CH:5][CH:4]=[C:3]([OH:2])[N:8]=2)[N:9]=[CH:10][C:11]=1[C:17](=[O:19])[CH3:18]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 24477Sodium ThiosulfateHCID 178471946HCID 178471946, compound

Product 1

HCID 1784671601-(4,6-Dihydroxy-1,5-naphthyridin-3-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of ethyl 2-[(6-methoxypyridin-3-ylamino)methylene]-3-oxobutanoate (70 g, 0.32 mol) in acetonitrile (800 ml) was added trimethylsilylchloride (173 g, 1.6 mol) and sodium iodide (140 g, 0.96 mol) and the reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature and satd. aq. sodium thiosulfate was added. The mixture was concentrated to remove acetonitrile, diluted with brine and the solids were filtered and dried to provide the intermediate 1-(4,6-dihydroxy-1,5-naphthyridin-3-yl)ethanone. This intermediate was suspended in dichloroethane (350 mL) followed by the addition of phosphorus oxychloride (200 mL) and catalytic N,N-dimethylformamide and the reaction mixture was stirred with heat at 80° C. for 3 h. The reaction mixture was cooled to room temperature and quenched by pouring slowly into ice-cold satd. aq. sodium bicarbonate or 3 N sodium hydroxide. The quenched reaction mixture was concentrated to remove the dichloroethane and the resulting solids were collected by filtration and purified by chromatography (silica, hexanes/ethyl acetate) to provide the desired product (50 g, 74% over 2 steps) as a brown solid: 1H NMR (300 MHz, CDCl3) δ 9.00 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 4.30 (q, J=7.1 Hz, 2H), 3.28-3.18 (m, 1H), 1.36 (t, J=7.1 Hz, 3H), ESI MS m/z 241 [M+H]+.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. concentrationThe mixture was concentrated
  4. customto remove acetonitrile
  5. additiondiluted with brine
  6. filtrationthe solids were filtered
  7. customdried

Sources & evidence

ORD record
ord-aaa428e33b2f4bb682d1eb81159975c4
Source dataset
uspto-grants-2015_06
Patent number
US09067937B2

Reaction notes

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