Hydrochloric Acid → 6-(7-Oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yloxy)quinoline-3-carboxylic acid

HRID 1894975Notes

Reaction equation

F[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C:6](=[O:12])[NH:7]2.[OH:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[CH:19][C:18]([C:24]([OH:26])=[O:25])=[CH:17]2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>O.CN(C)C=O>[O:12]=[C:6]1[NH:7][C:8]2[N:9]=[CH:10][CH:11]=[C:2]([O:13][C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][C:18]([C:24]([OH:26])=[O:25])=[CH:17]4)[C:3]=2[CH2:4][CH2:5]1

Participants

Conditions

Temperature: 150 °C

Procedure

5-fluoro-3,4-dihydro-1,8-naphthyridin-2(1H)-one (Int-28, 120 mg, 0.72 mmol), 6-hydroxyquinoline-3-carboxylic acid (1.5 mg, 0.794 mmol), and cesium carbonate (706 mg, 2.17 mmol) were weighed into a microwave vial. N,N-Dimethylformamide (3.5 mL) was added and the vial was sealed and heated in a microwave at 150° C. for 4 h. The vial was opened and water was added (5 mL). The resulting clear solution was neutralized by the addition of 1N HCl and washed with ethyl acetate. The washed aqueous phase was acidified to pH 3 and pure product was collected by suction filtration. LC-MS: (FA) ES+ 336; 1H NMR (400 MHz, d6-DMSO) δ ppm 13.55 (s, 1H), 10.60 (s, 1H), 9.27 (d, J=2.1 Hz, 1H), 8.94 (d, J=1.9 Hz, 1H), 8.17 (d, J=9.1 Hz, 1H), 8.07-8.02 (m, 1H), 7.85 (d, J=2.7 Hz, 1H), 7.74 (dd, J=9.1, 2.8 Hz, 1H), 6.52 (d, J=5.7 Hz, 1H), 2.92 (t, J=7.7, 7.7 Hz, 2H), 2.54 (dd, J=8.3, 7.1 Hz, 2H).

Workup

customthe vial was sealed
washwashed with ethyl acetate
filtrationwas collected by suction filtration

Sources & evidence

ORD record: ord-f4faa32bd88f41e898094011fa21f497
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513421B2

Reaction notes

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