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

HRID 1669050Notes

Reaction equation

[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:25]=[C:24]4[C:20]([CH2:21][CH2:22][CH2:23]4)=[CH:19][C:17]=3[N:18]=2)[CH2:5][CH2:4]1.CO.CC[O:31]C(C)=O>>[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[N:14]=[N+:15]([O-:26])[C:16]3[CH:25]=[C:24]4[C:20]([CH2:21][CH2:22][CH2:23]4)=[CH:19][C:17]=3[N+:18]=2[O-:31])[CH2:5][CH2:4]1

Participants

Reactant 2

HCID 11951466N-[3-(4-Methoxy-1-piperidinyl)propyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide

HCID 21584119Ethylacetate methanol

Product 1

HCID 135526557n-[3-(4-Methoxy-1-piperidinyl)propyl]-7,8-dihydro-6h-indeno[5,6-e][1,2,4]triazin-3-amine 1,4-dioxide

Procedure

H2O2 (70%, 0.92 mL, ca. 18.3 mmol) was added dropwise to a stirred solution of TFM (2.6 mL, 18.3 mmol) in DCM (20 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 58 (655 mg, 1.8 mmol) and TFA (0.71 mL, 9.2 mmol) in DCM (20 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 (0-10%) of MeOH/DCM, to give (i) starting material 58 (360 mg, 55%) and (ii) 1,4-dioxide 59 (213 mg, 31%) as a red solid: mp (MeOH/EtOAc) 128-130° C.; 1H NMR δ 8.42 (br s, 1H, NH), 8.11 (s, 1H, H-9), 8.10 (s, 1H, H-5), 3.62-3.68 (m, 2H, CH2N), 3.28-3.36 (m, 4H, OCH3, CHO), 3.08 (dt, J=7.5, 1.1 Hz, 2H, H-6), 3.03 (dt, J=7.5, 1.1 Hz, 2H, H-8), 2.69-2.76 (m, 2H, CH2N), 2.55 (br t, J=6.2 Hz, 2H, CH2N), 2.26-2.34 (m, 2H, CH2N), 2.17 (p, J=7.5 Hz, 2H, H-7), 1.94-2.03 (m, 2H, CH2), 1.88 (p, J=6.2 Hz, 2H, CH2), 1.72-1.81 (m, 2H, CH2); 13C NMR δ 155.4, 149.5, 145.5, 138.1, 129.5, 115.7, 111.7, 75.8, 57.2, 55.4, 50.8 (2), 41.6, 33.3, 32.3, 30.3 (2), 25.5, 25.1. Anal. calcd for C19H27N5O3.H2O: C, 58.3; H, 7.5; N, 17.9. Found: C, 58.4; H, 6.8; N, 17.6%.

Sources & evidence

ORD record: ord-f0949739382e48b798af491da1207054
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989451B2

Reaction notes

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