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

HRID 385649Notes

Reaction equation

HRID 385649 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([BH3-])#N.[Na+].[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[CH3:37])[CH:32]=O.C[O-].[Na+].CO.C(=O)([O-])O.[Na+]>CO.C(O)(=O)C>[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[CH3:37])[CH2:32][NH:2][CH:3]1[CH2:4][CH2:5][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])[CH2:7][CH2:8]1

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 27745743-Fluoro-4-methylbenzaldehyde2×HCID 5003444Sodium cyanoborohydride2×HCID 23694274Sodium methanolate methanolHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 441939891-(2-(4-((3-fluoro-4-methylbenzyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a suspension of 0.22 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride in 7 mL of methanol, 66 mg of sodium cyanoborohydride, 64 μL of 3-fluoro-4-methylbenzaldehyde, 0.30 g of a 28% sodium methoxide/methanol solution and 30 μL of acetic acid were added, and the mixture was stirred at room temperature for 3 hours. Thereto was added 22 mg of 3-fluoro-4-methylbenzaldehyde, and the mixture was stirred at the same temperature for 1 hour. Thereto was further added 33 mg of sodium cyanoborohydride, and the mixture was stirred at the same temperature for 1 hour. A saturated aqueous sodium hydrogen carbonate solution was added thereto, and the solvent was distilled off under reduced pressure. Thereto was added chloroform, 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 sequentially 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 an eluent of chloroform:methanol=9:1 to obtain 20 mg of 1-(2-(4-((3-fluoro-4-methylbenzyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one as a colorless oily substance.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at the same temperature for 1 hour
  3. stirringthe mixture was stirred at the same temperature for 1 hour
  4. distillationthe solvent was distilled off under reduced pressure
  5. additionThereto was added chloroform
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with chloroform
  8. washthe resultant solution was washed sequentially with water
  9. dry with materiala saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe resultant residue was purified by basic silica gel column chromatography

Sources & evidence

ORD record
ord-7d0c2a152bca41959b77803a34bde223
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

Loading…