Diphosgene → 6-chloro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

HRID 901252Notes

Reaction equation

HRID 901252 reaction equation
ClC(OC(Cl)(Cl)Cl)=[O:3].[CH3:9][O:10][C:11](=[O:29])[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[N:14][C:13]=1[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1>O1CCOCC1>[Cl:18][C:16]1[CH:15]=[N:14][C:13]2[N:19]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[C:9](=[O:3])[O:10][C:11](=[O:29])[C:12]=2[CH:17]=1

Participants

4

Reactant 2

HCID 10426DiphosgeneHCID 542852255-Chloro-2-(4-methoxy-benzylamino)-nicotinic Acid Methyl Ester

Product 1

HCID 596996046-chloro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dioneYield 91%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Trichloromethyl chloroformate (5.40 mL, 44.82 mmol) was added slowly to a solution of 5-chloro-2-(4-methoxy-benzylamino)-nicotinic acid methyl ester (72) (12.5 g, 40.75 mmol) in dioxane and refluxed for 4 h under nitrogen atmosphere. The solution was cooled and the solvent was removed under vacuum. The residue was recrystallized by ether to yield 11.80 g (91%) of 6-chloro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione (73) as white solids. MP: 173° C.; 1H-NMR (DMSO-d6): 3.71 (s, 3H), 5.25 (s, 2H), 6.85 (m, 2H), 7.33 (m, 2H), 8.49 (d, J=2.8 Hz, 1H), 8.82 (d, J=2.8 Hz, 1H); EIMS: 319 (M+1).

Workup

  1. temperaturerefluxed for 4 h under nitrogen atmosphere
  2. temperatureThe solution was cooled
  3. customthe solvent was removed under vacuum
  4. customThe residue was recrystallized by ether

Sources & evidence

ORD record
ord-9eaeed0cea1e43628c7702d166a43e66
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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