Cesium carbonate → Methyl 2-(4-bromo-5,7-difluoro-3-methylquinolin-2-ylamino)acetate

HRID 1431650Notes

Reaction equation

C(C1CCCCC1=O)(=O)C(C)C.Cl.[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH2:18].Br[C:21]1[C:30]([CH3:31])=[C:29]([Br:32])[C:28]2[C:23](=[CH:24][C:25]([F:34])=[CH:26][C:27]=2[F:33])[N:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.[Cu]I>[Br:32][C:29]1[C:28]2[C:23](=[CH:24][C:25]([F:34])=[CH:26][C:27]=2[F:33])[N:22]=[C:21]([NH:18][CH2:17][C:16]([O:15][CH3:14])=[O:19])[C:30]=1[CH3:31]

Participants

Conditions

Temperature: 70 °C

Procedure

2-Isobutyrylcyclohexanone (0.086 mL, 0.51 mmol), glycine methyl ester hydrochloride (480 mg, 3.9 mmol), 2,4-dibromo-5,7-difluoro-3-methylquinoline (870 mg, 2.6 mmol), copper(I) iodide (24 mg, 0.13 mmol) and cesium carbonate (2.5 g, 7.70 mmol) were slurried in DMF (3.0 mL) and stirred in an oil bath at 70° C. for 2 h. Another aliquot of copper(I) iodide (24 mg, 0.13 mmol) and 2-isobutyryl-cyclohexanone (0.086 mL, 0.51 mmol) were added and heated for an additional 1.5 h. No further progress was observed. The reaction mixture was then diluted with water and extracted with EtOAc (2×100 mL). The combined organic layers were washed with 1N lithium chloride (1×50 mL) and brine (1×50 mL) and dried over magnesium sulfate. The residue was then purified by medium pressure chromatography (silica gel, 0 to 40% EtOAc:hexanes) to give methyl 2-(4-bromo-5,7-difluoro-3-methylquinolin-2-ylamino)acetate. Mass Spectrum (ESI) m/e=347.0 (M+1).

Workup

temperatureheated for an additional 1.5 h
extractionextracted with EtOAc (2×100 mL)
washThe combined organic layers were washed with 1N lithium chloride (1×50 mL) and brine (1×50 mL)
dry with materialdried over magnesium sulfate
customThe residue was then purified by medium pressure chromatography (silica gel, 0 to 40% EtOAc:hexanes)

Sources & evidence

ORD record: ord-87ac670275734f00ac54395ac4d1797d
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

Loading…