Sodium Bicarbonate → 1-(2-(4-(((5-fluoro-6-methoxypyridin-3-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

HRID 385676Notes

Reaction equation

HRID 385676 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.[F:29][C:30]1[C:31]([O:38][CH3:39])=[N:32][CH:33]=[C:34]([CH:37]=1)[CH:35]=O.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(Cl)(Cl)Cl.C(O)(=O)C>[F:29][C:30]1[CH:37]=[C:34]([CH2:35][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)[CH:33]=[N:32][C:31]=1[O:38][CH3:39]

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride2×HCID 23694274Sodium methanolate methanolHCID 447547845-Fluoro-6-methoxypyridine-3-carbaldehydeHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 441937831-(2-(4-(((5-fluoro-6-methoxypyridin-3-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-oneYield 45.4%

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 and 28 μL of acetic acid were added. Thereto was added 75 mg of 5-fluoro-6-methoxynicotinaldehyde, then, 61 mg of sodium cyanoborohydride was added thereto, and the mixture was stirred at room temperature for 1 hour 20 minutes. Thereto was further added 62 mg of sodium cyanoborohydride, and the mixture was stirred at room temperature for 1 hour 30 minutes, and then stirred at 30 to 35° C. for 1 hour. To the reaction mixture, chloroform and a saturated aqueous sodium hydrogen carbonate solution were added. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was 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 9:1, diethyl ether was added to the resultant light yellow oily substance, and the solid was filtered off to obtain 97 mg of 1-(2-(4-(((5-fluoro-6-methoxypyridin-3-yl)methyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one as a slightly yellow solid.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at room temperature for 1 hour 30 minutes
  3. stirringstirred at 30 to 35° C. for 1 hour
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with chloroform
  6. washthe resultant solution was washed with water
  7. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe resultant residue was purified by basic silica gel column chromatography
  10. washelution with chloroform
  11. additionmethanol=19:1 to 9:1, diethyl ether was added to the resultant light yellow oily substance
  12. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-0a59443978fb42c8ae0cd163f020ac9e
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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