Dimethylformamide → 4-(5-fluoro-2-(2-fluorophenyl)-3-methyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide

HRID 1618646노트

반응식

HRID 1618646 반응식
[N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13][NH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CN(C=O)C.[H-].[Na+].Cl[C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][C:35]=2[F:37])[N:30]=[C:29]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[F:44])[C:28]=1[CH3:45]>CCOC(C)=O>[F:37][C:35]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:36]=1[C:27]([N:12]1[C:11]3[CH:18]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[CH:8]=[CH:9][C:10]=3[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13]1)=[C:28]([CH3:45])[C:29]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[F:44])=[N:30]2

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 596314454-Chloro-5-fluoro-2-(2-fluorophenyl)-3-methylquinolineHCID 672847356-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide

생성물 1

HCID 672854054-(5-fluoro-2-(2-fluorophenyl)-3-methyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

Under a N2 atmosphere, 6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide (0.0800 g, 0.298 mmol) was dissolved in DMF (2.00 mL, 26.0 mmol). Sodium hydride (0.0143 g, 0.596 mmol) was added and the reaction was allowed to stir at rt for 10 minutes. 4-Chloro-5-fluoro-2-(2-fluorophenyl)-3-methylquinoline (0.0950 g, 0.328 mmol) was added and the reaction was heated to 140° C. for 2 h. The reaction was diluted with EtOAc and washed with 2% sodium bicarbonate, then brine. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by preparative reverse phase chromatography to afford 4-(5-fluoro-2-(2-fluorophenyl)-3-methyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide. Mass Spectrum (ESI) m/e=522.2 (M+1)

후처리

  1. temperaturethe reaction was heated to 140° C. for 2 h
  2. washwashed with 2% sodium bicarbonate
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by preparative reverse phase chromatography

출처 및 근거

ORD 기록
ord-30d66cd1ae454bb198af751546ea4dfe
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

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