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

HRID 1669029Notes

Reaction equation

HRID 1669029 reaction equation
[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][NH2:11])[CH2:5][CH2:4]1.Cl[C:13]1[N:14]=[N+:15]([O-:26])[C:16]2[CH:25]=[C:24]3[C:20]([CH2:21][CH2:22][CH2:23]3)=[CH:19][C:17]=2[N:18]=1.CCN(CC)CC>COCCOC>[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][NH:11][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

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 47120352-(4-Methoxy-piperidin-1-yl)-ethylamineHCID 160813203-Chloro-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-Oxide

Product 1

HCID 11951117N-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-OxideYield 79%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Crude 2-(4-methoxy-1-piperidinyl)ethylamine (288) (3.8 g, 23.9 mmol) was added to a stirred solution of chloride 21 (1.77 g, 8.0 mmol) and Et3N (2.2 mL, 16.0 mmol) in DME (80 mL) and the solution stirred at reflux temperature for 6 h. The solvent was evaporated and the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL). The 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 1-oxide 42 (2.16 g, 79%) as a yellow solid: mp (MeOH/EtOAc) 131-133° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.39 (s, 1H, H-5), 5.82 (br s, 1H, NH), 3.50-3.56 (m, 2H, CH2N), 3.33 (s, 3H, OCH3), 3.21-3.26 (m, 1H, CHO), 2.97-3.03 (m, 4H, H-6, H-8), 2.72-2.82 (m, 2H, CH2N), 2.60 (dd, J=6.0, 5.8 Hz, 2H, CH2N), 2.20-2.26 (m, 2H, CH2N), 2.15 (br p, J=7.4 Hz, 2H, H-7), 1.84-1.92 (m, 2H, CH2), 1.57-1.65 (m, 2H, CH2); 13C NMR δ 158.7, 154.5, 148.8, 143.2, 129.8, 120.5, 114.7, 76.2, 56.3, 55.5, 50.7 (2), 38.2, 33.1, 32.3, 30.8 (2), 25.7. Anal. calcd for C18H25N5O2: C, 63.0; H, 7.3; N, 20.4. Found: C, 63.0; H, 7.4; N, 20.4%.

Workup

  1. temperatureat reflux temperature for 6 h
  2. customThe solvent was evaporated
  3. customthe residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL)
  4. customThe organic fraction was dried
  5. customthe solvent evaporated
  6. customThe residue was purified by chromatography
  7. washeluting with a gradient (0-15%) of MeOH/DCM

Sources & evidence

ORD record
ord-d2e6a381b2b847daadd9f3dd406a91a4
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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