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Acetic Acid → 6-[(4R)-4-{[3-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847093
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Reaktionsgleichung

Reaktionsgleichung von HRID 1847093
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([N:7]=[CH:8][C:9](=[O:17])[N:10]2[CH2:13][CH2:14][CH:15]=O)=[CH:5][CH:4]=1.[NH2:18][C@H:19]1[CH2:23][N:22]([C:24]2[CH:25]=[CH:26][C:27]3[O:28][CH2:29][C:30](=[O:34])[NH:31][C:32]=3[N:33]=2)[C:21](=[O:35])[CH2:20]1.C(OC(=O)N[C@@H]1CC(=O)NC1)(C)(C)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([N:7]=[CH:8][C:9](=[O:17])[N:10]2[CH2:13][CH2:14][CH2:15][NH:18][C@H:19]2[CH2:23][N:22]([C:24]3[CH:25]=[CH:26][C:27]4[O:28][CH2:29][C:30](=[O:34])[NH:31][C:32]=4[N:33]=3)[C:21](=[O:35])[CH2:20]2)=[CH:5][CH:4]=1
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Komponenten

8

Edukt 6

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 71301758(R)-tert-Butyl (5-oxopyrrolidin-3-yl)carbamateHCID 867249283-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)propanalHCID 867249916-[(4R)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Produkt 1

HCID 601616416-[(4R)-4-{[3-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

In N,N-dimethylformamide (5 ml) was dissolved 3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal (Reference Example 8,200 mg, 0.86 mmol). 6-[(4R)-4-Amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (synthesized using [(3R)-5-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester synthesized with reference to WO2004/22536 in the same manner as in Reference Examples 20, 21 and 22; 262 mg, 1.03 mmol) was added thereto and subsequently acetic acid (65 mg, 1.12 mmol) was added. The obtained mixture was stirred at room temperature for 1 hour, cooled on ice and sodium triacetoxyborohydride (237 mg, 1.12 mmol) was added thereto. After stirring at room temperature for 2 hours, sodium hydrogen carbonate aqueous solution was added thereto and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and a saturated sodium chloride solution, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The obtained crude product was purified by thin layer chromatography (dichloromethane/methanol) to yield 80 mg (20%) of the title compound.

Aufarbeitung

  1. customsynthesized with reference to WO2004/22536 in the same manner as in Reference Examples 20, 21 and 22
  2. addition262 mg, 1.03 mmol) was added
  3. additionwas added
  4. stirringAfter stirring at room temperature for 2 hours
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe obtained organic layer was washed with water
  7. dry with materiala saturated sodium chloride solution, dried over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe obtained crude product
  10. customwas purified by thin layer chromatography (dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-5ca51d6c92fd4a6bb9d67e07736b4561
Quelldatensatz
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08952010B2

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