3-Methoxybenzylamine → 1-(4-Methoxy-benzylamino)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029106Notes

Reaction equation

HRID 1029106 reaction equation
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2.CO[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH2:23].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[C:62](C)([O-:64])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:62][O:64][C:26]1[CH:19]=[CH:20][C:21]([CH2:22][NH:23][C:2]2[CH:11]=[CH:10][N:9]=[C:8]3[C:3]=2[C:4]2[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=2[C:6](=[O:12])[NH:7]3)=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 211563-MethoxybenzylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 581680081-Chlorobenzo[C][1,8]naphthyridin-6(5H)-one

Product 1

HCID 581682611-(4-Methoxy-benzylamino)-5H-benzo[c][1,8]naphthyridin-6-oneYield 16%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (40 mg, 0.22 mmol), 3-methoxybenzylamine (48 mg, 0.35 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (7 mg, 0.02 mmol), and sodium tert-butoxide (67 mg, 0.69 mmol) were suspended in dioxane (2 mL), and stirred overnight at 100° C. The reaction mixture was concentrated, partitioned between H2O/EtOAc, and filtered. The precipitate was washed with H2O/EtOAc, and suspended in MeOH. 2M HCl/ether was added and the resulting mixture was filtered. The precipitate (Pd salts) was washed with MeOH, and the filtrate was concentrated. The crude product was purified via prep-LC-MS. The purified product was converted to the HCl salt via dissolving in MeOH, addition of 2 M HCl, and evaporation. The resulting precipitate was triturated from CH2Cl2, filtered, and dried under vacuum to provide 97 (10 mg, 16% yield) as a yellow solid. LC-MS (M+H=332, obsd.=332). 1H NMR (400 MHz, d6-DMSO): δ 9.10 (s, 1H), 8.63 (d, 1H), 8.38 (d, 1H), 8.08 (d, 1H), 7.98 (t, 1H), 7.71 (m, 2H), 7.29 (t, 1H), 7.05 (m, 2H), 6.87 (dd, 1H), 6.74 (d, 1H), 4.76 (d, 2H), 3.72 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between H2O/EtOAc
  3. filtrationfiltered
  4. washThe precipitate was washed with H2O/EtOAc
  5. addition2M HCl/ether was added
  6. filtrationthe resulting mixture was filtered
  7. washThe precipitate (Pd salts) was washed with MeOH
  8. concentrationthe filtrate was concentrated
  9. customThe crude product was purified via prep-LC-MS
  10. dissolutionvia dissolving in MeOH
  11. additionaddition of 2 M HCl, and evaporation
  12. customThe resulting precipitate was triturated from CH2Cl2
  13. filtrationfiltered
  14. customdried under vacuum

Sources & evidence

ORD record
ord-4e980197c96740d8bbaa4bf78424211b
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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