Sodium cyanoborohydride → 1-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride

HRID 385666Notes

Reaction equation

HRID 385666 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]([F:21])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:22])[CH2:5][CH2:4]1.[O:23]1[C:28]2=[CH:29][N:30]=[C:31]([CH:33]=O)[CH:32]=[C:27]2[CH2:26][CH2:25][CH2:24]1.C([BH3-])#N.[Na+].C[O-].[Na+].CO>CO.C(OCC)(=O)C.C(O)(=O)C>[ClH:1].[O:23]1[C:28]2=[CH:29][N:30]=[C:31]([CH2:33][NH:2][CH:3]3[CH2:4][CH2:5][N:6]([CH2:9][CH2:10][N:11]4[C:20]5[C:15](=[N:16][CH:17]=[C:18]([F:21])[CH:19]=5)[CH:14]=[CH:13][C:12]4=[O:22])[CH2:7][CH2:8]3)[CH:32]=[C:27]2[CH2:26][CH2:25][CH2:24]1

Participants

8

Reactant 4

HCID 5003444Sodium cyanoborohydrideHCID 23694274Sodium methanolate methanolHCID 566403113,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehydeHCID 689271131-(2-(4-aminopiperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride

Product 1

HCID 689273251-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochlorideYield 75.8%

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-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride and 61 mg of 3,4-dihydro-2H-pyrano(2,3-c)pyridine-6-carbaldehyde in 2.5 mL of methanol, 62 mg of sodium cyanoborohydride, 0.14 g of a 28% sodium methoxide/methanol solution and 86 μL of acetic acid were added, and the mixture was stirred at room temperature for 1 hour 50 minutes. Thereto were added ethyl acetate, a saturated aqueous sodium hydrogen carbonate solution, and a 2 mol/L aqueous sodium hydroxide solution, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate twice. The organic layer and the extract were combined, the resultant solution was 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 1 mL of methanol and 1 mL of and ethyl acetate, and thereto was added 0.5 mL of a 4 mol/L hydrogen chloride/ethyl acetate solution at room temperature. The solvent was distilled off under reduced pressure, diethyl ether was added the resultant residue, and the solid was filtered off to obtain 0.11 g of 1-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride as a light yellow solid.

Workup

  1. additionwere added
  2. customa saturated aqueous sodium hydrogen carbonate solution, and a 2 mol/L aqueous sodium hydroxide solution, the organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate twice
  4. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried 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. dissolutionThe resultant residue was dissolved in 1 mL of methanol
  9. addition1 mL of and ethyl acetate, and thereto was added 0.5 mL of a 4 mol/L hydrogen chloride/ethyl acetate solution at room temperature
  10. distillationThe solvent was distilled off under reduced pressure, diethyl ether
  11. additionwas added the resultant residue
  12. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-0fa878553d6d4447985d0d7d2221ce9f
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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