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

HRID 1847017Notes

Reaction equation

HRID 1847017 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:14][CH2:15][CH:16]=O)[C:10](=[O:13])[CH:11]=[CH:12][C:6]2=[N:5][CH:4]=1.[NH2:18][CH:19]1[CH2:23][N:22]([C:24]2[CH:25]=[CH:26][C:27]3[O:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=3[CH:34]=2)[C:21](=[O:35])[CH2:20]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][C:3]1[N:8]=[C:7]2[N:9]([CH2:14][CH2:15][CH2:16][NH:18][CH:19]3[CH2:20][C:21](=[O:35])[N:22]([C:24]4[CH:25]=[CH:26][C:27]5[O:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=5[CH:34]=4)[CH2:23]3)[C:10](=[O:13])[CH:11]=[CH:12][C:6]2=[N:5][CH:4]=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 867249463-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl)propanal

Product 1

HCID 601619133-Methoxy-5-(3-{[5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]amino}propyl)pyrido[2,3-b]pyrazin-6 (5H)-oneYield 29.3%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

3-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl)propanal (292 mg, 1.25 mmol) and 6-(4-amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 310 mg, 1.25 mmol) were dissolved in a mixed solvent (33 ml) of dichloromethane/N,N-dimethylformamide (10:1). Acetic acid (0.143 ml, 2.50 mmol) and anhydrous sodium sulfate (600 mg) were added to the solution and the mixture was stirred at room temperature for 13 hours. Sodium triacetoxyborohydride (531 mg, 2.50 mmol) was added to the reaction solution, the mixture was stirred for 4 hours and the solvent was removed under reduced pressure. A lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue, the resultant was alkalized by adding saturated sodium bicarbonate water under cooling on ice and extracted with a lower layer solvent of chloroform/methanol/water (7:3:1). After drying the extract with anhydrous sodium sulfate, the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol) to yield 170 mg (29%) of the title compound in the form of a white solid.

Workup

  1. stirringthe mixture was stirred for 4 hours
  2. customthe solvent was removed under reduced pressure
  3. additionA lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue
  4. additionby adding saturated sodium bicarbonate water
  5. temperatureunder cooling on ice
  6. extractionextracted with a lower layer solvent of chloroform/methanol/water (7:3:1)
  7. customAfter drying the
  8. extractionextract with anhydrous sodium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-4c80def0190f47d2881c8b1a2e88e38c
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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