Sodium Sulfate → 6-Methoxy-4-(4-{[5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]amino}butyl)pyrido[2,3-b]pyrazin-3(4H)-one

HRID 1847040Notes

Reaction equation

HRID 1847040 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:22]=[CH:23][C:24]2[N:29]=[CH:28][C:27](=[O:30])[N:26]([CH2:31][CH2:32][CH2:33][CH:34]=O)[C:25]=2[N:36]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O.ClCCl>[CH3:19][O:20][C:21]1[CH:22]=[CH:23][C:24]2[N:29]=[CH:28][C:27](=[O:30])[N:26]([CH2:31][CH2:32][CH2:33][CH2:34][NH:1][CH:2]3[CH2:3][C:4](=[O:18])[N:5]([C:7]4[CH:8]=[CH:9][C:10]5[O:15][CH2:14][C:13](=[O:16])[NH:12][C:11]=5[CH:17]=4)[CH2:6]3)[C:25]=2[N:36]=1

Participants

8

Reactant 5

HCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 824984066-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneHCID 867249644-(6-Methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)butanal

Product 1

HCID 601616436-Methoxy-4-(4-{[5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]amino}butyl)pyrido[2,3-b]pyrazin-3(4H)-oneYield 18.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In N,N-dimethylformamide (5 ml) were dissolved 6-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 148 mg, 0.60 mmol) and 4-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)butanal (148 mg, 0.60 mmol). Sodium sulfate (1.0 g) was added to this solution and the mixture was stirred overnight at room temperature. Sodium triacetoxyborohydride (508 mg, 2.40 mmol) was added to the reaction solution and the mixture was stirred at room temperature for 6 hours. After completion of the reaction, the reaction solution was diluted with dichloromethane, basified by adding a saturated sodium hydrogen carbonate aqueous solution, and the organic layer was then separated and washed in the order of saturated sodium chloride solution, water (3×) and saturated sodium chloride solution. 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 53 mg (18%) of the title compound in the form of a light yellow foamy solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 6 hours
  2. customAfter completion of the reaction
  3. customthe organic layer was then separated
  4. washwashed in the order of saturated sodium chloride solution, water (3×) and saturated sodium chloride solution
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-1955345b3da24db6987f4b72db334365
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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