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

HRID 385658Notes

Reaction equation

HRID 385658 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.C([BH3-])#N.C([BH3-])#N.[Na+].[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][C:33]=1[CH3:40].C[O-].[Na+].CO.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(OCC)(=O)C.C(O)(=O)C>[ClH:1].[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][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:34][C:33]=1[CH3:40]

Participants

10

Reactant 6

HCID 516892Sodium BicarbonateHCID 27348744-Fluoro-3-methylbenzaldehyde3×HCID 5003444Sodium cyanoborohydrideHCID 23694274Sodium methanolate methanolHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochlorideHCID 131729803Sodium cyanoborohydride cyanoborohydride2×

Product 1

HCID 689292391-(2-(4-((4-fluoro-3-methylbenzyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 0.10 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride in 4 mL of methanol, 31 mg of sodium cyanoborohydride cyanoborohydride, 44 μL of 4-fluoro-3-methylbenzaldehyde, 39 mg of a 28% sodium methoxide/methanol solution and 42 μL of acetic acid were added, and the mixture was stirred at room temperature for 1 hour 15 minutes. Thereto were added 44 μL of 4-fluoro-3-methylbenzaldehyde and 31 mg of sodium cyanoborohydride cyanoborohydride, and the mixture was stirred at the same temperature for 45 minutes. Thereto were further added 44 μL of 4-fluoro-3-methylbenzaldehyde and 31 mg of sodium cyanoborohydride, and the mixture was stirred at the same temperature for 30 minutes. A saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added thereto, and the organic layer was separated, 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. The resultant residue was dissolved in 2 mL of ethyl acetate, and thereto was added 1 mL of a 4.0 mol/L hydrogen chloride/ethyl acetate solution at room temperature. The solvent was distilled off under reduced pressure, ethyl acetate was added to the resultant residue and the solid was filtered off to obtain 54 mg of 1-(2-(4-((4-fluoro-3-methylbenzyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride as a light yellow solid.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at the same temperature for 45 minutes
  3. stirringthe mixture was stirred at the same temperature for 30 minutes
  4. customthe organic layer was separated
  5. washwashed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe resultant residue was purified by basic silica gel column chromatography
  9. dissolutionThe resultant residue was dissolved in 2 mL of ethyl acetate
  10. additionwas added 1 mL of a 4.0 mol/L hydrogen chloride/ethyl acetate solution at room temperature
  11. distillationThe solvent was distilled off under reduced pressure, ethyl acetate
  12. additionwas added to the resultant residue
  13. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-5f0974c6b0b64fa782a3d92889967a33
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

Loading…