Sodium triacetoxyborohydride → 6-[(4S)-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 1847014Notes

Reaction equation

HRID 1847014 reaction equation
[NH2:1][C@@H:2]1[CH2:6][N:5]([C:7]2[CH:8]=[CH:9][C:10]3[O:11][CH2:12][C:13](=[O:17])[NH:14][C:15]=3[N:16]=2)[C:4](=[O:18])[CH2:3]1.[CH3:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([N:25]=[CH:26][C:27](=[O:35])[N:28]2[CH2:31][CH2:32][CH:33]=O)=[CH:23][CH:22]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[CH3:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([N:25]=[CH:26][C:27](=[O:35])[N:28]2[CH2:31][CH2:32][CH2:33][NH:1][C@@H:2]2[CH2:6][N:5]([C:7]3[CH:8]=[CH:9][C:10]4[O:11][CH2:12][C:13](=[O:17])[NH:14][C:15]=4[N:16]=3)[C:4](=[O:18])[CH2:3]2)=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 867249283-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)propanalHCID 867249446-[(4S)-4-Amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Product 1

HCID 601616426-[(4S)-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)-oneYield 32%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

6-[(4S)-4-Amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (94.1 mg, 0.379 mol) and 3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal (Reference Example 8; 106 mg, 0.456 mmol) were dissolved in chloroform/methanol (10:1, v/v, 6 ml). Molecular sieve 3 A (powder, 1.0 g) was added to the solution and heated under reflux for 3 hours. After cooling, sodium triacetoxyborohydride (145 mg, 0.684 mmol) was added to the reaction mixture and the mixture was stirred overnight at room temperature. After completion of the reaction, the molecular sieve was removed by filtration and a saturated sodium hydrogen carbonate aqueous solution was added to the filtrate and stirred. After separating the organic layer, the aqueous layer was extracted twice with chloroform/methanol (10:1, v/v) and combined with the organic layer. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was purified by thin-layer chromatography (chloroform/methanol) to yield 56 mg (32%) of the title compound in the form of a colorless solid.

Workup

  1. additionMolecular sieve 3 A (powder, 1.0 g) was added to the solution
  2. temperatureheated
  3. temperatureunder reflux for 3 hours
  4. temperatureAfter cooling
  5. customAfter completion of the reaction
  6. customthe molecular sieve was removed by filtration
  7. additiona saturated sodium hydrogen carbonate aqueous solution was added to the filtrate
  8. stirringstirred
  9. customAfter separating the organic layer
  10. extractionthe aqueous layer was extracted twice with chloroform/methanol (10:1
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. customthe solvent was removed under reduced pressure
  13. customThe obtained residue was purified by thin-layer chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-fe5e929efae44f66a1ce69e28aa8a645
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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