P-Anisidine → 8,9-dimethoxy-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029080Notes

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.C[O:18][C:19]1C=CC(N)=CC=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:16]1[C:2]([O:18][CH3:19])=[CH:3][C:4]2[C:13]3[C:8](=[N:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6](=[O:14])[C:5]=2[CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

9-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (30 mg, 0.13 mmol), 4-methoxy-aniline (24 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 28 (20 mg, 43% yield) as a yellow solid. LC-MS (M+H=318, obsd.=318). 1H NMR (400 MHz, d6-DMSO): δ 11.60 (s, 1H), 8.44 (dd, 1H), 8.39 (dd, 1H), 8.09 (d, 1H), 7.68 (d, 1H), 7.23 (m, 3H), 7.14 (dd, 1H), 6.97 (m, 2H), 3.77 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-ab58b5ee16c64f26a36f8d06b14985a2
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735584B2

Reaction notes

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