3-Fluoroaniline → 9-(2-Methoxy-phenylamino)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029081Notes

Reaction equation

HRID 1029081 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:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[C:60](C)([O-:62])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:60][O:62][C:22]1[CH:23]=[CH:24][CH:18]=[CH:19][C:20]=1[NH:21][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 97423-FluoroanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 581682989-chloro-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 581681599-(2-Methoxy-phenylamino)-5H-benzo[c][1,8]naphthyridin-6-oneYield 41.2%

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 (30 mg, 0.13 mmol), 3-fluoro-aniline (22 mg, 0.20 mmol), palladium(II) acetate (1 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (5 mg, 0.015 mmol), and sodium tert-butoxide (38 mg, 0.39 mmol) were suspended in dioxane (1 mL), and stirred overnight at 100° C. The reaction mixture was added directly to a Biotage column. The crude product was purified via Biotage silica-gel chromatography eluting with a gradient of 0 to 10% MeOH in CH2Cl2. The recovered product was converted to the HCl salt via suspending in CH2Cl2, addition of 2 M HCl/ether, filtering the resulting precipitate, and washing with CH2Cl2 to provide 30 (17 mg, 38% yield) as a yellow solid. LC-MS (M+H=306, obsd.=306). 1H NMR (400 MHz, d6-DMSO): δ 11.73 (s, 1H), 8.55 (dd, 1H), 8.47 (dd, 1H), 8.19 (d, 1H), 7.95 (d, 1H), 7.38 (m, 2H), 7.29 (dd, 1H), 7.12 (dd, 1H), 7.07 (m, 1H), 6.80 (dt, 1H).

Workup

  1. additionThe reaction mixture was added directly to a Biotage column
  2. customThe crude product was purified via Biotage silica-gel chromatography
  3. washeluting with a gradient of 0 to 10% MeOH in CH2Cl2
  4. additionaddition of 2 M HCl/ether
  5. filtrationfiltering the resulting precipitate
  6. washwashing with CH2Cl2

Sources & evidence

ORD record
ord-0d5d0372f1c74095b82a7b6187cdfcde
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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