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

HRID 1618729Notes

Reaction equation

HRID 1618729 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:20]3[CH2:25][CH2:24]S[C:22]4[N:26]=[CH:27][C:28]([N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)=[CH:29][C:21]3=4)=[C:7]([CH3:19])[C:8]([C:12]3[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.O.OO.[OH:39][S:40]([O-:42])=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:20]3[CH2:25][CH2:24][S:40](=[O:42])(=[O:39])[C:22]4[N:26]=[CH:27][C:28]([N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)=[CH:29][C:21]3=4)=[C:7]([CH3:19])[C:8]([C:12]3[CH:17]=[C:16]([CH3:18])[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 672849584-(1-(7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

Product 1

HCID 672848091-(7-fluoro-3-methyl-2-(4-methyl-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-(4-methylpyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine (45 mg, 0.09 mmol) in EtOAc (2.5 mL) was added disodium tungstate (30.4 mg, 0.092 mol) and water (0.5 mL). The reaction was cooled at 0° C. and then H2O2 (56.6 μL, 1.85 mmol, 30%) was added. The reaction was allowed to warm to rt for 1 h. After this time more disodium tungstate (10 mg) was added followed by H2O2 (0.5 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-(4-methyl-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 8.59 (1H, d, J=4.7 Hz), 7.86-7.91 (2H, m), 7.70-7.77 (2H, m), 7.38 (1H, ddd, J=9.2, 8.0, 2.5 Hz), 7.25 (1H, dd, J=5.0, 0.9 Hz), 5.58 (1H, d, J=2.5 Hz), 4.18-4.27 (2H, m), 3.59-3.75 (6H, m), 2.84-3.02 (4H, m), 2.51 (3H, s), 2.44 (3H, s). Mass Spectrum (ESI) m/e=520.0 (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-87b10e7eeef54894b1bbcd9644e97080
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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