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

HRID 1431650ノート

反応式

HRID 1431650 の反応式
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]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 122755Glycine methyl ester hydrochlorideHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-one2 回HCID 596311142,4-Dibromo-5,7-difluoro-3-methylquinoline

生成物 1

HCID 59631255Methyl 2-(4-bromo-5,7-difluoro-3-methylquinolin-2-ylamino)acetate

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒2 回HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-87ac670275734f00ac54395ac4d1797d
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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