2-Methoxyethylamine → 9-morpholin-4-yl-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029079Notes

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.[CH3:17][O:18][CH2:19][CH2:20][NH2:21].[CH:22]1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:21]1([C:2]2[CH:16]=[CH:15][C:5]3[C:6](=[O:14])[NH:7][C:8]4[C:13]([C:4]=3[CH:3]=2)=[CH:12][CH:11]=[CH:10][N:9]=4)[CH2:22][CH2:17][O:18][CH2:19][CH2:20]1

Participants

Conditions

Temperature: 100 °C

Procedure

9-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (50 mg, 0.22 mmol), 2-methoxy-ethylamine (24 mg, 0.33 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (8 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 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 to provide 26 (20 mg, 34% yield) as a white solid. LC-MS (M+H=270, obsd.=270). 1H NMR (400 MHz, d6-DMSO): δ 11.48 (s, 1H), 8.67 (d, 1H), 8.42 (dd, 1H), 7.98 (d, 1H), 7.38 (d, 1H), 7.24 (dd, 1H), 6.95 (dd, 1H), 6.67 (t, 1H), 3.55 (t, 2H), 3.42 (t, 2H), 3.30 (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

Sources & evidence

ORD record: ord-1372608fe0644e9a90afed2807d01b97
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735584B2

Reaction notes

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