Acetic Acid → 6-[(4R)-4-({[2-(Methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847054Notes

Reaction equation

HRID 1847054 reaction equation
[CH3:1][O:2][CH2:3][O:4][CH:5]([CH2:8][N:9]1[C:14](=[O:15])[CH:13]=[N:12][C:11]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[N:19][C:10]1=2)[CH:6]=O.[NH2:22][CH2:23][C@@H:24]1[CH2:28][N:27]([C:29]2[CH:30]=[CH:31][C:32]3[O:33][CH2:34][C:35](=[O:39])[NH:36][C:37]=3[N:38]=2)[C:26](=[O:40])[CH2:25]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:14](=[O:15])[CH:13]=[N:12][C:11]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[N:19][C:10]1=2)[CH2:6][NH:22][CH2:23][C@@H:24]1[CH2:28][N:27]([C:29]2[CH:30]=[CH:31][C:32]3[O:33][CH2:34][C:35](=[O:39])[NH:36][C:37]=3[N:38]=2)[C:26](=[O:40])[CH2:25]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 867249736-[(4R)-4-(Aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 867249792-(methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal

Product 1

HCID 867249806-[(4R)-4-({[2-(Methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

In a mixed solvent (6 ml) of dichloromethane/N,N dimethylformamide (5:1) were dissolved 2-(methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal (as 0.217 mmol) and 6-[(4R)-4-(aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 54; 57 mg, 0.217 mmol). Acetic acid (0.025 ml, 0.434 mmol) and anhydrous sodium sulfate (100 mg) were added to the solution and the mixture was stirred at room temperature for 14 hours. Sodium triacetoxyborohydride (92 mg, 0.434 mmol) was added to the reaction solution, the mixture was stirred for 8 hours and then 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 41 mg (35%) of the title compound in the form of an orange oily product.

Workup

  1. stirringthe mixture was stirred for 8 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-8b1453b2ddc344dbb50eb49542d0ee55
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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