Methyl iodide → 8-Fluoro-6-(4-fluoro-phenyl)-2-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 925681노트

반응식

HRID 925681 반응식
[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][NH:20][C:21](=[O:22])[C:6]3=[CH:5][C:4]=2[CH:3]=1.[H-].[Na+].I[CH3:26]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][N:20]([CH3:26])[C:21](=[O:22])[C:6]3=[CH:5][C:4]=2[CH:3]=1

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 900360598-Fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

생성물 1

HCID 900358568-Fluoro-6-(4-fluoro-phenyl)-2-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one수율 40%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of 8-fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 18) (0.05 g, 0.17 mmol) in DMF (1.1 ml) was added at room temperature sodium hydride (8.78 mg, 0.2 mmol), and the mixture was allowed to stir at room temperature for 30 min. Afterwards iodomethane (23.8 mg, 10.5 μl, 0.17 mmol) was added and the reaction mixture was allowed to stir at room temperature for 16 h. The mixture was poured into ice/water (30 ml) and extracted with ethyl acetate (2×25 ml). The combined organic layers were washed with brine (25 ml), dried (MgSO4) and evaporated. The crude product (50 mg) was further purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (0-50%)] to yield the title compound as a white solid (21 mg, 40%), MS (ISP) m/z=313.4 [(M+H)+], mp 212° C.

후처리

  1. stirringto stir at room temperature for 16 h
  2. extractionextracted with ethyl acetate (2×25 ml)
  3. washThe combined organic layers were washed with brine (25 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product (50 mg) was further purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (0-50%)]

출처 및 근거

ORD 기록
ord-35211e7b08744a9e9ac3e9c6c338cc13
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284321B2

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