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

HRID 385672Notes

Reaction equation

HRID 385672 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][N:6]=[C:5]([CH:10]=O)[CH:4]=1.C[O-].[Na+].CO.Cl.[NH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][N:27]2[C:36]3[C:31](=[N:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=3)[CH:30]=[CH:29][C:28]2=[O:39])[CH2:21][CH2:20]1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(Cl)(Cl)Cl.C(O)(=O)C>[CH3:38][O:37][C:34]1[CH:35]=[C:36]2[C:31]([CH:30]=[CH:29][C:28](=[O:39])[N:27]2[CH2:26][CH2:25][N:22]2[CH2:21][CH2:20][CH:19]([NH:18][CH2:10][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([CH3:9])=[CH:7][N:6]=3)[CH2:24][CH2:23]2)=[N:32][CH:33]=1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 23694274Sodium methanolate methanolHCID 578154004-Methoxy-5-methylpyridine-2-carbaldehydeHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 578151937-methoxy-1-(2-(4-(((4-methoxy-5-methylpyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-oneYield 63.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 71 mg of 4-methoxy-5-methylpyridine-2-carbaldehyde in 2 mL of methanol, 0.27 g of a 28% sodium methoxide/methanol solution, 0.19 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride and 27 μL of acetic acid were added. Then, 59 mg of sodium cyanoborohydride was added thereto and the mixture was stirred at room temperature for 4 hours. 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=19:1 to 86:14 to obtain 0.13 g of 7-methoxy-1-(2-(4-(((4-methoxy-5-methylpyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one as a yellow oily substance.

Workup

  1. customThe organic layer was separated
  2. washwashed with water
  3. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe resultant residue was purified by basic silica gel column chromatography
  6. washelution with chloroform

Sources & evidence

ORD record
ord-0d7c1424627041f9bfb695443b0cd96f
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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