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

HRID 1431650노트

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HRID 1431650 반응식
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]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 122755Glycine methyl ester hydrochlorideHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-one2회HCID 596311142,4-Dibromo-5,7-difluoro-3-methylquinoline

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매2회HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-87ac670275734f00ac54395ac4d1797d
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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