4-Fluorobenzylamine → 9-(3-Methoxy-benzylamino)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029090Notes

Reaction equation

HRID 1029090 reaction equation
Cl[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.F[C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[C:61](C)([O-:63])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:61][O:63][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:18]=1)[CH2:22][NH:23][C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3

Participants

7

Reactant 4

HCID 673264-FluorobenzylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 581682989-chloro-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 581683119-(3-Methoxy-benzylamino)-5H-benzo[c][1,8]naphthyridin-6-oneYield 27.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

9-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (50 mg, 0.22 mmol), 4-fluoro-benzylamine (54 mg, 0.43 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (10 mg, 0.02 mmol), and sodium tert-butoxide (63 mg, 0.65 mmol) were suspended in dioxane (2 mL), and stirred overnight at 100° C. The reaction mixture was concentrated, diluted with H2O/EtOAc, and filtered. The precipitate was washed with EtOAc/H2O and purified via prep-LC-MS. The purified product was converted to the HCl salt via dissolving in MeOH, addition of 1 M HCl/ether, and concentration. The HCl salt was triturated in CH2Cl2, filtered, washed with CH2Cl2, and dried under vacuum to provide 42 (20 mg, 26% yield) as a yellow solid. LC-MS (M+H=320, obsd.=320). 1H NMR (400 MHz, d6-DMSO): δ 11.48 (s, 1H), 8.58 (d, 1H), 8.42 (dd, 1H), 7.99 (d, 1H), 7.48 (m, 3H), 7.38 (d, 1H), 7.24 (m, 2H), 7.18 (m, 2H), 6.94 (d, 1H), 4.49 (s, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with H2O/EtOAc
  3. filtrationfiltered
  4. washThe precipitate was washed with EtOAc/H2O
  5. custompurified via prep-LC-MS
  6. dissolutionvia dissolving in MeOH
  7. additionaddition of 1 M HCl/ether, and concentration
  8. customThe HCl salt was triturated in CH2Cl2
  9. filtrationfiltered
  10. washwashed with CH2Cl2
  11. customdried under vacuum

Sources & evidence

ORD record
ord-1bd1c2d6aa9c47f6ab91edcd11cae529
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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