Sodium Bicarbonate → 6-(((1-(2-(7-methoxy-2-oxoquinoxaline-1-(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-1,4-benzooxazine-3(4H)-one

HRID 39819Notes

Reaction equation

HRID 39819 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]=[C:24]1[NH:29][C:28]2[CH:30]=[C:31]([CH:34]=O)[CH:32]=[CH:33][C:27]=2[O:26][CH2:25]1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(OCC)(=O)C.C(O)(=O)C.CO>[CH3:21][O:20][C:17]1[CH:18]=[C:19]2[C:14]([N:13]=[CH:12][C:11](=[O:22])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][CH:2]([NH:1][CH2:34][C:31]3[CH:32]=[CH:33][C:27]4[O:26][CH2:25][C:24](=[O:23])[NH:29][C:28]=4[CH:30]=3)[CH2:7][CH2:6]2)=[CH:15][CH:16]=1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 107736383-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbaldehydeHCID 593978381-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinoxalin-2(1H)-one

Product 1

HCID 593984256-(((1-(2-(7-methoxy-2-oxoquinoxaline-1-(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-1,4-benzooxazine-3(4H)-oneYield 19.2%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 3.0 mL of a methanol solution containing 0.20 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one, 0.12 g of 3-oxo-3,4-dihydro-2H-1,4-benzooxazine-6-carbaldehyde, 38 μL of acetic acid and 83 mg of sodium cyanoborohydride were added at room temperature and stirred at the same temperature for 6.5 hours. To the reaction mixture, chloroform and aqueous saturated sodium hydrogen carbonate solution were added to be adjusted to pH 10.2, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed sequentially with water and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=5:1], diethyl ether was added to the foam thus obtained, and the resulting solid was filtered to afford a yellow solid. To this solid, ethyl acetate and chloroform were added, the mixture was cooled to the room temperature after heating, and the resulting solid was filtered to give 59 mg of 6-(((1-(2-(7-methoxy-2-oxoquinoxaline-1-(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-1,4-benzooxazine-3(4H)-one a pale yellow solid.

Workup

  1. additionwere added at room temperature
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted with chloroform
  4. washwashed sequentially with water and aqueous saturated sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified by silica gel column chromatography [eluent; chloroform:methanol=5:1], diethyl ether
  9. additionwas added to the foam
  10. customthus obtained
  11. filtrationthe resulting solid was filtered
  12. customto afford a yellow solid
  13. temperatureafter heating
  14. filtrationthe resulting solid was filtered

Sources & evidence

ORD record
ord-9b4844dff8574c9a9a3220e659c387c0
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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