N-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide → n-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6h-indeno[5,6-e][1,2,4]triazin-3-amine 1,4-dioxide

HRID 1669031Notes

Reaction equation

[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([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)[CH2:5][CH2:4]1.CO.CC[O:30]C(C)=O>>[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([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-:30])[CH2:5][CH2:4]1

Participants

Reactant 2

HCID 11951117N-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide

HCID 21584119Ethylacetate methanol

Product 1

HCID 135526548n-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6h-indeno[5,6-e][1,2,4]triazin-3-amine 1,4-dioxide

Procedure

H2O2 (70%, 3.1 mL, ca. 62.6 mmol) was added dropwise to a stirred solution of TFAA (8.8 mL, 62.6 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 42 (2.15 g, 6.3 mmol) and TFA (2.4 mL, 31.3 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 20° C. for 8 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give (i) starting material 42 (204 mg, 9%); and (ii) 1,4-dioxide 43 (1.0 g, 44%) as a red solid: mp (MeOH/EtOAc) 148-151° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.10 (s, 1H, H-5), 7.44 (br s, 1H, NH), 3.61-3.66 (m, 2H, CH2N), 3.33 (s, 3H, OCH3), 3.22-3.29 (m, 1H, CHO), 3.10 (br t, J=7.5 Hz, 2H, H-6), 3.05 (br t, J=7.5 Hz, 2H, H-8), 2.75-2.81 (m, 2H, CH2N), 2.68 (br t, J=6.0 Hz, 2H, CH2N), 2.27-2.34 (m, 2H, CH2N), 2.20 (p, J=7.5 Hz, 2H, H-7), 1.87-1.95 (m, 2H, CH2), 1.61-1.70 (m, 2H, CH2); 13C NMR δ 155.6, 149.4, 145.8, 138.0, 129.7, 115.7, 111.6, 75.8, 56.3, 55.5, 50.7 (2), 38.3, 33.4, 32.4, 30.6 (2), 25.6. Anal. calcd for C18H25N5O3.¼H2O: C, 59.4; H, 7.1; N, 19.2. Found: C, 59.2; H, 6.8; N, 19.1%.

Sources & evidence

ORD record: ord-9348bf6ff6624d95ba7a41563b241d5a
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989451B2

Reaction notes

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