Sodium Bicarbonate → 1-(2-(4-(((5-ethylpyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

HRID 385671Notes

Reaction equation

HRID 385671 reaction equation
Cl.[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.C[O-].[Na+].CO.[CH2:29]([C:31]1[CH:32]=[CH:33][C:34]([CH:37]=O)=[N:35][CH:36]=1)[CH3:30].C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(Cl)(Cl)Cl.C(O)(=O)C>[CH2:29]([C:31]1[CH:32]=[CH:33][C:34]([CH2:37][NH:2][CH:3]2[CH2:4][CH2:5][N:6]([CH2:9][CH2:10][N:11]3[C:20]4[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:23])[CH2:7][CH2:8]2)=[N:35][CH:36]=1)[CH3:30]

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride2×HCID 127523665-Ethylpyridine-2-carbaldehydeHCID 23694274Sodium methanolate methanolHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 578153551-(2-(4-(((5-ethylpyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-oneYield 72.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a suspension of 0.20 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride in 2 mL of methanol, 0.28 g of a 28% sodium methoxide/methanol solution, 66 mg of 5-ethylpyridine-2-carbaldehyde and 28 μL of acetic acid were added. Then, 61 mg of sodium cyanoborohydride was added thereto and the mixture was stirred at room temperature for 3 hours. Thereto was further added 31 mg of sodium cyanoborohydride, and the mixture was stirred at room temperature for 1 hour 30 minutes. To the reaction mixture, chloroform and a saturated aqueous sodium hydrogen carbonate solution were added. The organic layer was separated, washed with water and 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 gradient elution with chloroform:methanol=93:7 to 9:1 to obtain 0.15 g of 1-(2-(4-(((5-ethylpyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one as a light yellow oily substance.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at room temperature for 1 hour 30 minutes
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resultant residue was purified by basic silica gel column chromatography
  8. washelution with chloroform

Sources & evidence

ORD record
ord-478e6ae5a6ea4b669ff29deceac8723e
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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