Hydrochloric Acid → 9-benzyloxy-7-bromo-2-(3-chlorobenzyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione

HRID 1349487Notes

Reaction equation

HRID 1349487 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][NH:6][C:7]([C:9]1[N:10]([CH2:25][CH2:26]O)[CH:11]=[C:12]([Br:24])[C:13](=[O:23])[C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:8].C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.Cl>O1CCCC1>[CH2:16]([O:15][C:14]1[C:13](=[O:23])[C:12]([Br:24])=[CH:11][N:10]2[CH2:25][CH2:26][N:6]([CH2:5][C:4]3[CH:28]=[CH:29][CH:30]=[C:2]([Cl:1])[CH:3]=3)[C:7](=[O:8])[C:9]=12)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 588591603-Benzyloxy-5-bromo-1-(2-hydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide

Product 1

HCID 230776699-benzyloxy-7-bromo-2-(3-chlorobenzyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dioneYield 93.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Benzyloxy-5-bromo-1-(2-hydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (1.75 g) was suspended in tetrahydrofuran (50 ml), and N,N-diisopropylethylamine (3.72 ml) and methanesulfonyl chloride (1.38 ml) were added. After stirring at room temperature for 1 hr, 0.5N aqueous hydrochloric acid (40 ml) was added, and the mixture was extracted twice with ethyl acetate (100 ml each). The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate, dried and concentrated. The obtained residue was dissolved in dimethylformamide (50 ml) and 60% sodium hydride was added by small portions with stirring at room temperature. After confirming the completion of the reaction by thin layer chromatography (TLC), the reaction mixture was ice-cooled, 0.33N aqueous hydrochloric acid (300 ml) was added, and the mixture was extracted twice with ethyl acetate (250 ml each). The ethyl acetate layer was washed with water, dried, concentrated, and crystallized from ethyl acetate-hexane to give 9-benzyloxy-7-bromo-2-(3-chlorobenzyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione (1.58 g).

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate (100 ml each)
  2. washThe ethyl acetate layer was washed with aqueous sodium hydrogen carbonate
  3. customdried
  4. concentrationconcentrated
  5. dissolutionThe obtained residue was dissolved in dimethylformamide (50 ml)
  6. addition60% sodium hydride was added by small portions
  7. stirringwith stirring at room temperature
  8. customthe completion of the reaction by thin layer chromatography (TLC)
  9. temperaturecooled
  10. extractionthe mixture was extracted twice with ethyl acetate (250 ml each)
  11. washThe ethyl acetate layer was washed with water
  12. customdried
  13. concentrationconcentrated
  14. customcrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-71dbec66bf254048a1658b561d42290c
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

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