Hydrogen Peroxide → 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-7-(4-morpholinyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine 4,4-dioxide

HRID 1618727Notes

Reaction equation

HRID 1618727 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[CH2:24][CH2:23]S[C:21]4[N:25]=[CH:26][C:27]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)=[CH:28][C:20]3=4)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.O.OO.[OH:38][S:39]([O-:41])=O.[Na+]>CCOC(C)=O.[O-][W]([O-])(=O)=O.[Na+].[Na+]>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[CH2:24][CH2:23][S:39](=[O:41])(=[O:38])[C:21]4[N:25]=[CH:26][C:27]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)=[CH:28][C:20]3=4)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 784Hydrogen Peroxide2×HCID 962WaterHCID 23665763Sodium BisulfiteHCID 672846194-(1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

Product 1

HCID 672847431-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-7-(4-morpholinyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine 4,4-dioxide

Reagents, catalysts & solvents 2

HCID 26052Sodium tungstateCatalyst2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine (40 mg, 0.084 mmol) in EtOAc (2.5 mL) was added disodium tungstate (24.8 mg, 0.084 mol) and water (0.3 mL). The reaction was cooled at 0° C. and then H2O2 (25.9 μL, 0.84 mmol, 30%) was added. The reaction was allowed to warm to rt for 1 h. After this time more disodium tungstate (7 mg) was added followed by H2O2 (0.4 mL, 30%) and the reaction was stirred at rt overnight. After this time the reaction was diluted with EtOAc (50 mL) and treated with a saturated aqueous solution of NaHSO3 (15 mL). The separated organic layer was washed with brine (15 mL), dried over MgSO4, filtered and evaporated in vacuo to give 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-7-(4-morpholinyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine 4,4-dioxide. 1H NMR (400 MHz, chloroform-d) δ ppm 8.64-8.81 (1H, m), 7.87-7.95 (4H, m), 7.74 (1H, dd, J=9.1, 5.8 Hz), 7.36-7.45 (2H, m), 5.59 (1H, s), 4.21-4.26 (2H, m), 3.63-3.72 (6H, m), 2.88-3.01 (4H, m), 2.46 (3H, s). Mass Spectrum (ESI) m/e=506.0 (M+1).

Workup

  1. temperatureto warm to rt for 1 h
  2. washThe separated organic layer was washed with brine (15 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-362a7f5993844ec09576a533bbbe11bf
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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