Pyridine → Ethyl 3-amino-7-bromo-6-fluoroquinoline-2-carboxylate

HRID 924379Notes

Reaction equation

[N:1]1C=CC=CC=1.Br[CH2:8][C:9](=O)[C:10]([O:12][CH2:13][CH3:14])=[O:11].[NH2:16][C:17]1[CH:24]=[C:23]([Br:25])[C:22]([F:26])=[CH:21][C:18]=1[CH:19]=O.N1CCCC1>CCO>[NH2:1][C:8]1[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:16][C:17]2[C:18]([CH:19]=1)=[CH:21][C:22]([F:26])=[C:23]([Br:25])[CH:24]=2

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of pyridine (310.6 mg, 3.927 mmol) in EtOH (8.0 mL), a solution of ethyl bromopyruvate (752.1 mg, 3.857 mmol) in EtOH (8.0 mL) was added dropwise over a period of 20 min. The mixture was heated to 65° C. for 1 h, and then cooled to room temperature. 2-Amino-4-bromo-5-fluorobenzaldehyde (796.1 mg, 3.651 mmol) was added, followed by pyridine (690.6 mg, 8.731 mmol). The mixture was heated at 85° C. for 5 h. Pyrrolidine (640.1 mg, 9.000 mmol) was then added. After heating for an additional 3 h, the reaction mixture was allowed to cool and was then concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-100% EtOAc in hexanes) to give the sub-title compound as a yellow solid (882.5 mg, 77%). LCMS calc. for C12H11BrFN2O2(M+H)+: m/z=313.0. found 313.0.

Workup

temperaturecooled to room temperature
temperatureThe mixture was heated at 85° C. for 5 h
temperatureAfter heating for an additional 3 h
temperatureto cool
concentrationwas then concentrated under reduced pressure
customThe residue was purified by flash chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b9eb4234058c48df80dd6055bb325eb8
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278950B2

Reaction notes

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