Hydrogen Peroxide → N-[2-(4-Morpholinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1,4-Dioxide

HRID 1669033Notes

Reaction equation

HRID 1669033 reaction equation
OO.[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N:17]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C([O-])([O-])=[O:27].[Na+].[Na+]>C(O)(C(F)(F)F)=O.O>[N:3]1([CH2:9][CH2:10][NH:11][C:12]2[N:13]=[N+:14]([O-:25])[C:15]3[CH:24]=[C:23]4[C:19]([CH2:20][CH2:21][CH2:22]4)=[CH:18][C:16]=3[N+:17]=2[O-:27])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 784Hydrogen Peroxide2×HCID 10340Sodium CarbonateHCID 11951284N-[2-(4-Morpholinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide

Product 1

HCID 135526549N-[2-(4-Morpholinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1,4-DioxideYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
20 °C

Procedure

H2O2 (70%, 0.50 mL, ca. 10.0 mmol) was added to a stirred solution of 1-oxide 44 (3.00 g, 9.52 mmol) in a mixture of TFA (30 mL) and water (2 mL) at 20° C. Ten more aliquots of 70% H2O2 (0.5 mL) were added in 30 min intervals and the reaction mixture was stirred at 20° C. for 26 h. Water (100 mL) was added and the mixture made basic with Na2CO3. The mixture was extracted with DCM (4×200 mL) and the combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of MeOH/DCM, to give 1,4-dioxide 45 (1.13 g, 36%) as a red solid: 1H NMR δ 8.13 (s, 1H, H-9), 8.10 (s, 1H, H-5), 7.38 (br s, 1H, NH), 3.73 (t, J=4.5 Hz, 4H, CH2O), 3.67 (m, 2H, CH2N), 3.03-3.15 (m, 4H, H-6, H-8), 2.68 (t, J=6.0 Hz, 2H, CH2N), 2.53 (t, J=4.5 Hz, 4H, CH2N), 2.17-2.25 (m, 2H, H-7); 13C NMR δ 155.7, 149.4, 145.9, 137.9, 129.7, 115.8, 111.6, 65.9 (2), 56.8, 53.4 (2), 37.7, 33.4, 32.4, 25.6. The hydrochloride salt was crystallised as a red solid: mp (MeOH/DCM) 184-185° C. Anal. calcd for C16H21N5O3.¾HCl: C, 53.5; H, 6.2; N, 19.5. Found: C, 53.9; H, 6.3; N, 19.6%.

Workup

  1. extractionThe mixture was extracted with DCM (4×200 mL)
  2. customthe combined organic fraction was dried
  3. customthe solvent evaporated
  4. customThe residue was purified by chromatography
  5. washeluting with a gradient (0-5%) of MeOH/DCM

Sources & evidence

ORD record
ord-33e1f8a657284135a87981db8b8aae67
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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