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

HRID 1847091Notes

Reaction equation

HRID 1847091 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[N:15]=[CH:14][C:13](=[O:16])[N:12]([CH2:17][CH2:18][CH:19]=O)[C:11]=2[N:21]=1.[NH2:22][C@@H:23]1[CH2:27][N:26]([C:28]2[CH:29]=[CH:30][C:31]3[O:32][CH2:33][C:34](=[O:38])[NH:35][C:36]=3[N:37]=2)[C:25](=[O:39])[CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[N:15]=[CH:14][C:13](=[O:16])[N:12]([CH2:17][CH2:18][CH2:19][NH:22][C@@H:23]3[CH2:27][N:26]([C:28]4[CH:29]=[CH:30][C:31]5[O:32][CH2:33][C:34](=[O:38])[NH:35][C:36]=5[N:37]=4)[C:25](=[O:39])[CH2:24]3)[C:11]=2[N:21]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 867249446-[(4S)-4-Amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 867249613-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal

Product 1

HCID 601620496-[(4S)-4-{[3-(6-Methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 11.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Acetic acid (0.06 g, 1 mmol) was added dropwise to a mixture of 3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal (synthesized with reference to WO2008/9700; 0.2 g, 0.85 mmol), 6-[(4S)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 22; 0.25 g, 1.0 mmol) and N,N-dimethylformamide (4 ml). Sodium triacetoxyborohydride (0.23 g, 1.1 mmol) was gradually added under cooling on ice to the obtained mixture, which was then stirred for 10 minutes. The mixture was further stirred at room temperature for 2 hours, cooled on ice, a saturated sodium hydrogen carbonate aqueous solution was added thereto, and the resultant was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (dichloromethane/methanol) to yield 45 mg (11%) of the title compound.

Workup

  1. temperatureunder cooling on ice to the obtained mixture, which
  2. stirringThe mixture was further stirred at room temperature for 2 hours
  3. temperaturecooled on ice
  4. extractionthe resultant was extracted with dichloromethane
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained crude product
  8. customwas purified by silica gel column chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-a805115b0c8f4623b5209fa75e1e5eff
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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