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 1618646Notes

Reaction equation

HRID 1618646 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-30d66cd1ae454bb198af751546ea4dfe
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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