Sulfuric Acid → 9-fluoro-6-isopropenylbenzo[c]-1,6-naphthyridin-1(2H)-one

HRID 2193029Notes

Reaction equation

C([O:5][C:6]1[N:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[C:8]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:9]=1[C:10]([C:16]([CH3:18])=[CH2:17])=[N:11]2)CCC.S(=O)(=O)(O)O.[OH-].[Na+]>O.CCOC(C)=O>[F:23][C:21]1[CH:20]=[CH:19][C:9]2[C:10]([C:16]([CH3:18])=[CH2:17])=[N:11][C:12]3[CH:13]=[CH:14][NH:15][C:6](=[O:5])[C:7]=3[C:8]=2[CH:22]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred suspension of 1-butoxy-9-fluoro-6-isopropenylbenzo[c]-1,6-naphthyridine (30 mg, 0.097 mmol) in water (0.5 ml) was added sulfuric acid (0.5 ml) (CAUTION: EXOTHERM). The reaction mixture was stirred for 15 h at 100° C. The reaction was diluted with EtOAc (30 mL) and water (30 mL). To the resulting biphasic mixture was added NaOH (0.85 g, 21 mmol) portionwise to make the aqueous layer basic. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude residue was dissolved in 3 ml DMF and 100 uL of TFA, and purified by preparative reverse phase HPLC eluting with an acetonitrile/water+(with 0.05% TFA as a modified) gradient, to afford 9-fluoro-6-isopropenylbenzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO-D6) δ 11.92 (br s, 1H), 9.74 (dd, 1H), 8.41 (dd, 1H), 7.64-7.60 (overlapping m, 2H), 6.78 (d, 1H), 5.70 (s, 1H), 5.22 (s, 1H), 2.25 (s, 3H). LRMS (ESI) calc'd for (C15H11FN2O) [M+H]+, 255.1; found 255.0.

Workup

dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
dissolutionThe crude residue was dissolved in 3 ml DMF
custom100 uL of TFA, and purified by preparative reverse phase HPLC
washeluting with an acetonitrile/water+(with 0.05% TFA as

Sources & evidence

ORD record: ord-5c69cba85cf94a19b60c4d7c96f518d4
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329722B2

Reaction notes

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