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

HRID 1349487노트

반응식

HRID 1349487 반응식
[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

참가 물질

6

반응물 4

HCID 313Hydrochloric Acid2회HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 588591603-Benzyloxy-5-bromo-1-(2-hydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-71dbec66bf254048a1658b561d42290c
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07211572B2

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