Hydrochloric Acid → 1,6-Naphthyridin-5-amine

HRID 1772018Notes

Reaction equation

HRID 1772018 reaction equation
[N:1]([C:4]1[N:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2)=[N+]=[N-].O.O.Cl[Sn]Cl.Cl.C([O-])(O)=O.[Na+]>CO>[N:9]1[C:10]2[CH:11]=[CH:12][N:13]=[C:4]([NH2:1])[C:5]=2[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 61436Stannous chloride dihydrateHCID 516892Sodium BicarbonateHCID 866678085-Azido-1,6-naphthyridine

Product 1

HCID 292496221,6-Naphthyridin-5-amineYield 81%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 5-azido-1,6-naphthyridine (3.2 g, 18.7 mmol) in MeOH (30 mL) was stirred at room temperature. SnCl2.2H2O (21 g, 93.6 mmol) was added to the mixture, followed by the addition of concentrated HCl (10 mL), then the mixture was refluxed for 5 h. The mixture was cooled to room temperature, and neutralized with sat. NaHCO3 to adjust the pH to 7-8. The mixture was filtered, and the aqueous phase was extracted with EtOAc (5×30 mL). The combined organic layers were dried with Na2SO4, filtered, and the solvent was removed under reduced pressure to yield 1,6-naphthyridin-5-amine as a pale yellow solid, which was used in the next step without further purification (2.20 g, yield 81%). ESI MS: m/z 146 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.91 (dd, 1J=1.6 Hz, 2J=4.8 Hz, 1H), 8.62 (d, J=8.0 Hz, 1H), 8.00 (d, J=6.0 Hz, 1H), 7.47 (dd, 1J=4.8 Hz, 2J=8.0 Hz, 1H), 7.09 (br, 2H), 6.98 (d, J=6.0 Hz, 1H).

Workup

  1. temperaturethe mixture was refluxed for 5 h
  2. filtrationThe mixture was filtered
  3. extractionthe aqueous phase was extracted with EtOAc (5×30 mL)
  4. dry with materialThe combined organic layers were dried with Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-751f684851e54d7c995ea19174d15f6b
Source dataset
uspto-grants-2016_02
Patent number
US09249162B2

Reaction notes

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