Piperidine → HCID 56837973, compound

HRID 2359341Notes

Reaction equation

HRID 2359341 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([NH2:14])=[O:13])[CH:8]=[CH:7]2.[NH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:15]1([C:2]2[CH:3]=[N:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([C:12]([NH2:14])=[O:13])[CH:8]=[CH:7]3)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 116732618-bromo-1,6-naphthyridine-2-carboxamide

Product 1

HCID 56837973HCID 56837973, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Conditions

Temperature
110 °C

Procedure

8-Bromo-1,6-naphthyridine-2-carboxamide (22.4 g, 99 mmol) produced in Example 12 (12a) was dissolved in piperidine (152 g, 1.78 mol), to which potassium carbonate (36.9 g, 267 mmol) and tetrabutylammonium iodide (TBAI) (11.8 g, 99 mmol) were then added, followed by stirring at 110° C. for four hours. Piperidine was distilled off under reduced pressure. Toluene and water were added to the residue thus obtained, and the resulting mixture was partitioned (the pH of the aqueous layer was adjusted to be weakly basic). The aqueous layer was extracted with dichloromethane again, and then combined with the toluene layer. The resulting mixture was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue thus obtained was sequentially purified by normal phase silica gel column chromatography ((after letting hexane:ethyl acetate, 50:50, flow through, applying ethyl acetate:methanol, 100:0-90:10, V/V), basic silica gel column chromatography (hexane:ethyl acetate, 100:0-0:100, V/V), and reverse phase silica gel column chromatography (water:acetonitrile, 90:10-60:40, V/V) to give the desired title compound (15.7 g, yield 69%).

Workup

  1. additionwere then added
  2. distillationPiperidine was distilled off under reduced pressure
  3. additionToluene and water were added to the residue
  4. customthus obtained
  5. customthe resulting mixture was partitioned (the pH of the aqueous layer
  6. extractionThe aqueous layer was extracted with dichloromethane again
  7. dry with materialThe resulting mixture was dried over anhydrous sodium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue thus obtained
  10. customwas sequentially purified by normal phase silica gel column chromatography ((after letting hexane:ethyl acetate, 50:50, flow through, applying ethyl acetate:methanol, 100:0-90:10, V/V), basic silica gel column chromatography (hexane:ethyl acetate, 100:0-0:100, V/V)

Sources & evidence

ORD record
ord-1389fb4ff1da4c69b3f3ecaa60cdd841
Source dataset
uspto-grants-2014_04
Patent number
US08685981B2

Reaction notes

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