Sodium triacetoxyborohydride → 6-(4-{[4-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)butyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one

HRID 1846995Notes

Reaction equation

HRID 1846995 reaction equation
[NH2:1][CH:2]1[CH2:6][N:5]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][C:13](=[O:16])[NH:12][C:11]=3[CH:17]=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:36])[N:28]2[CH2:31][CH2:32][CH2:33][CH:34]=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:36])[N:28]2[CH2:31][CH2:32][CH2:33][CH2:34][NH:1][CH:2]2[CH2:6][N:5]([C:7]3[CH:8]=[CH:9][C:10]4[O:15][CH2:14][C:13](=[O:16])[NH:12][C:11]=4[CH:17]=3)[C:4](=[O:18])[CH2:3]2)=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 824984066-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneHCID 867249234-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)butanal

Product 1

HCID 867249266-(4-{[4-(7-Methoxy-2-oxoquinoxalin-1(2H)-yl)butyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneYield 84.3%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
60 °C

Procedure

6-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (56.9 mg, 0.230 mmol) and 4-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)butanal (Reference Example 3; 56.6 mg, 0.230 mmol) were dissolved in chloroform/methanol (10:1, v/v, 3 ml), molecular sieve 3 A (powder 700 mg) was further added, and the mixture was stirred at 60° C. for 4.5 hours. After cooling, sodium triacetoxyborohydride (154 mg, 0.69 mmol) was added to the reaction solution and the mixture was stirred at room temperature for 1.5 hours. 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 silica gel column chromatography (chloroform/methanol) to yield 92.6 mg (84%) of the title compound in the form of a colorless solid.

Workup

  1. temperatureAfter cooling
  2. stirringthe mixture was stirred at room temperature for 1.5 hours
  3. customAfter completion of the reaction
  4. customthe molecular sieve was removed by filtration
  5. additiona saturated sodium hydrogen carbonate aqueous solution was added to the filtrate
  6. stirringstirred
  7. customAfter separating the organic layer
  8. extractionthe aqueous layer was extracted twice with chloroform/methanol (10:1
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-ce1406f1df0848eb9f566c344aa63b03
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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