Triethylamine → 6-Methoxy-8-piperazin-1-yl-[1,7]naphthyridine

HRID 428553Notes

Reaction equation

HRID 428553 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([NH2:13])[N:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.[CH3:14][CH2:15][N:16](CC)[CH2:17][CH3:18].[OH-].[Na+].C([O-])=O.[NH4+]>C(O)CCC.CCO.[Pd].O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[N:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 2723923Ammonium formateHCID 130013406-Methoxy-1,7-naphthyridin-8-amine

Product 1

HCID 184140846-Methoxy-8-piperazin-1-yl-[1,7]naphthyridineYield 8.6%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 2631-ButanolSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-methoxy-[1,7]naphthyridin-8-ylamine (2.25 g, 12.8 mmol), bis(2-chloroethyl)-benzlyamine (10.25 g, 38.6 mmol) and Et3N (5.34 mL, 38.6 mmol) in BuOH (100 mL) was heated at 100° C. for 72 hours. The cooled reaction mixture was poured into H2O (100 mL) and 2.5 N NaOH (100 mL), and extracted into EtOAc (2×200 mL). The organic phases were combined, dried over NASO4, filtered and concentrated. The resulting oil was purified twice by column chromatography (10% MeOH/CH2Cl2) affording a dark gold oil with BuOH impurity. This oil was dissolved in EtOH (50 mL) and 10% Pd/C (390 mg) and ammonium formate (730 mg) was added. The reaction mixture was heated at 80° C. for 2.5 hours. The cooled reaction mixture was filtered through a pad of celite and washed with EtOAc (50 mL). The organic phase was concentrated and purified by column chromatography (10% MeOH/CH2Cl2+NH4OH) affording 270 mg of the title compound as a dark orange oil. An analytical sample was prepared as the HCl salt from EtOAc.

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted into EtOAc (2×200 mL)
  3. customdried over NASO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting oil was purified twice by column chromatography (10% MeOH/CH2Cl2)
  7. customaffording a dark gold oil with BuOH impurity
  8. customThe cooled reaction mixture
  9. filtrationwas filtered through a pad of celite
  10. washwashed with EtOAc (50 mL)
  11. concentrationThe organic phase was concentrated
  12. custompurified by column chromatography (10% MeOH/CH2Cl2+NH4OH)

Sources & evidence

ORD record
ord-d05f3fe6b95d4a3d9b4b45657258983e
Source dataset
uspto-grants-2001_11
Patent number
US06313126B1

Reaction notes

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