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

HRID 2193193Notes

Reaction equation

HRID 2193193 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[S:26][CH2:25]1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.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[S: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

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 109433483-Oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carbaldehydeHCID 593978381-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinoxalin-2(1H)-one

Product 1

HCID 593983086-(((1-(2-(7-methoxy-2-oxoquinoxaline-1-(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-1,4-benzothiazine-3(4H)-oneYield 18.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To 3.0 mL of methanol solution containing 0.20 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one, 0.13 g of 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-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 4 hours. To the mixture, chloroform and aqueous saturated sodium hydrogen carbonate solution was added to be adjusted to pH 9.5, 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=20 3], to give 60 mg of 6-(((1-(2-(7-methoxy-2-oxoquinoxaline-1-(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-1,4-benzothiazine-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=20 3]

Sources & evidence

ORD record
ord-314ee3c22351435196ac4b33e40234e9
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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