Trifluoroacetic acid → 9-bromo-8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398384Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.FC(F)(F)C(O)=O.[Br:26]N1C(=O)CCC1=O>C(#N)C>[Br:26][C:3]1[C:2]([Cl:1])=[CH:18][C:6]2[N:7]([CH3:17])[C:8](=[O:16])[C:9]3[C:14]([C:5]=2[CH:4]=1)=[CH:13][CH:12]=[N:11][C:10]=3[CH3:15]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.2 g, 0.773 mmol) in acetonitrile (4 mL) at −30° C. was added trifluoroacetic acid (0.089 mL, 1.160 mmol) and 1-bromopyrrolidine-2,5-dione (0.151 g, 0.850 mmol). The mixture was heated to 80° C. overnight. The reaction mixture was concentrated, diluted with ethyl acetate and excess aqueous 10% NaHCO3. The ethyl acetate layer was concentrated. The residue was purified by prep. HPLC to afforded 9-bromo-8-chloro-4,6 dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (120 mg, 0.351 mmol, 45% yield) as white solid. LC/MS (ESI) m/e 337.0 [(M+H)+, calcd for C14H11BrClN2O, 337.0]; LC/MS retention time (Method C): tR=2.55 min; 1H NMR (400 MHz, METHANOL-d4) ppm 3.11 (s, 3H), 3.75 (s, 3H), 7.81 (s, 1H), 8.20-8.26 (m, 1H), 8.68 (d, J=5.6 Hz, 1H), 8.79 (s, 1H).

Workup

concentrationThe reaction mixture was concentrated
additiondiluted with ethyl acetate and excess aqueous 10% NaHCO3
concentrationThe ethyl acetate layer was concentrated
customThe residue was purified by prep

Sources & evidence

ORD record: ord-f123b5653669484bb070996b0a2bec07
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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