Sodium Hydroxide → 7-methoxy-1-(2-(4-((5,6,7,8-tetrahydroquinoxalin-2-ylmethyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochloride

HRID 1510749Notes

Reaction equation

HRID 1510749 reaction equation
[ClH:1].[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:23])[CH2:5][CH2:4]1.[N:24]1[C:33]2[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=2[N:27]=[CH:26][C:25]=1[CH:34]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].[OH-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O.C(N(CC)CC)C.C(O)(=O)C>[ClH:1].[CH3:22][O:21][C:18]1[CH:19]=[C:20]2[C:15]([CH:14]=[CH:13][C:12](=[O:23])[N:11]2[CH2:10][CH2:9][N:6]2[CH2:5][CH2:4][CH:3]([NH:2][CH2:34][C:25]3[CH:26]=[N:27][C:28]4[CH2:29][CH2:30][CH2:31][CH2:32][C:33]=4[N:24]=3)[CH2:8][CH2:7]2)=[N:16][CH:17]=1

Participants

11

Reactant 5

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 578154485,6,7,8-Tetrahydroquinoxaline-2-carbaldehydeHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 689255387-methoxy-1-(2-(4-((5,6,7,8-tetrahydroquinoxalin-2-ylmethyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochlorideYield 49.4%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.13 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride in 2.6 mL of N,N-dimethylformamide, 75 mg of 5,6,7,8-tetrahydroquinoxaline-2-carbaldehyde, 0.26 mL of acetic acid, 0.21 mL of triethylamine and 98 mg of sodium triacetoxyborohydride were added, and the mixture was stirred at room temperature for 9 hours 40 minutes. Thereto were added water, a saturated aqueous sodium hydrogen carbonate solution, and ethyl acetate, and the reaction mixture was adjusted to pH 11.5 with a 20% aqueous sodium hydroxide solution, the organic layer was then separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of chloroform:methanol=10:1, and thereto were added ethyl acetate and a 4 mol/L hydrogen chloride/ethyl acetate solution. The solvent was distilled off under reduced pressure, diethyl ether was added thereto, and the solid was filtered off to obtain 92 mg of 7-methoxy-1-(2-(4-((5,6,7,8-tetrahydroquinoxalin-2-ylmethyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochloride as a light brown solid.

Workup

  1. customthe organic layer was then separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resultant residue was purified by basic silica gel column chromatography
  7. additionmethanol=10:1, and thereto were added ethyl acetate
  8. distillationThe solvent was distilled off under reduced pressure, diethyl ether
  9. additionwas added
  10. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-8fce5743d68e44a4be4ebe5d78498132
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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