Acetic Acid → 6-(4-{[2-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one

HRID 1847004Notes

Reaction equation

HRID 1847004 reaction equation
[CH3:1][O:2][CH2:3][O:4][CH:5]([CH2:8][N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][C:10]1=[O:21])[CH:6]=O.[NH2:22][CH:23]1[CH2:27][N:26]([C:28]2[CH:29]=[CH:30][C:31]3[O:36][CH2:35][C:34](=[O:37])[NH:33][C:32]=3[CH:38]=2)[C:25](=[O:39])[CH2:24]1.C(O)(=O)C.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O>[CH3:1][O:2][CH2:3][O:4][CH:5]([CH2:8][N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][C:10]1=[O:21])[CH2:6][NH:22][CH:23]1[CH2:27][N:26]([C:28]2[CH:29]=[CH:30][C:31]3[O:36][CH2:35][C:34](=[O:37])[NH:33][C:32]=3[CH:38]=2)[C:25](=[O:39])[CH2:24]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 824984066-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneHCID 867249342-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal

Product 1

HCID 867249356-(4-{[2-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneYield 65%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

2-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal (0.340 mmol) and 6-(4-amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 84 mg, 0.340 mmol) were dissolved in a mixed solvent of dichloromethane/N,N-dimethylformamide (10:1,11 ml). Acetic acid (0.039 ml, 0.680 mmol) and anhydrous sodium sulfate (200 mg) were added to this solution, and the mixture was stirred at room temperature for two and a half hours. Sodium triacetoxyborohydride (144 mg, 0.680 mmol) was added thereto, the mixture was stirred for 14 hours and then the solvent was removed under reduced pressure. Chloroform was added to the residue, the resultant was alkalized by adding saturated sodium bicarbonate water under cooling on ice and extracted with chloroform. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to yield 115 mg (65%) of the title compound in the form of a colorless clear oily product.

Workup

  1. stirringthe mixture was stirred for 14 hours
  2. customthe solvent was removed under reduced pressure
  3. additionChloroform was added to the residue
  4. additionby adding saturated sodium bicarbonate water
  5. temperatureunder cooling on ice
  6. extractionextracted with chloroform
  7. dry with materialAfter drying over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-da98d35852c1437ebbffeb539c1f9480
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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