N-(3-Aminopropyl)morpholine → N-[3-(4-Morpholinyl)propyl]-7,8-dihydro-6H-chromeno[6,7-e][1,2,4]triazin-3-amine 1-Oxide

HRID 1669176Notes

Reaction equation

HRID 1669176 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][NH2:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[C:12]1[N:13]=[N+:14]([O-:26])[C:15]2[CH:25]=[C:24]3[C:19]([CH2:20][CH2:21][CH2:22][O:23]3)=[CH:18][C:16]=2[N:17]=1>COCCOC>[N:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:12]2[N:13]=[N+:14]([O-:26])[C:15]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH2:22][O:23]4)=[CH:18][C:16]=3[N:17]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 61055N-(3-Aminopropyl)morpholineHCID 251398843-Chloro-7,8-dihydro-6H-chromeno[6,7-e][1,2,4]triazine 1-Oxide

Product 1

HCID 25138863N-[3-(4-Morpholinyl)propyl]-7,8-dihydro-6H-chromeno[6,7-e][1,2,4]triazin-3-amine 1-OxideYield 93%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

3-(4-Morpholinyl)propylamine (0.71 mL, 4.8 mmol) was added to a stirred solution of chloride 240 (380 mg, 1.6 mmol) in DME (40 mL) and the solution stirred at reflux temperature for 4 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 (0-10%) of MeOH/DCM, to give 1-oxide 243 (514 mg, 93%) as a yellow solid: mp (MeOH/EtOAc) 151-152° C.; 1H NMR δ 7.60 (s, 1H, H-10), 7.30 (s, 1H, H-5), 6.00 (br s, 1H, NH), 4.26 (br dd, J=5.3, 5.2 Hz, 2H, H-8), 3.75 (br t, J=4.7 Hz, 4H, 2×CH2O), 3.55 (dt, J=6.3, 5.9 Hz, 2H, CH2N), 2.97 (br t, J=6.3 Hz, 2H, H-6), 2.45-2.52 (m, 6H, 3×CH2N), 2.02-2.08 (m, 2H, H-7), 1.79-1.86 (m, 2H, CH2); 13C NMR δ 158.1, 152.9, 143.6, 135.1, 130.0, 126.1, 104.4, 67.0 (2), 66.9, 57.3 (2), 53.8, 40.7, 25.9, 25.3, 21.7. Anal. calcd for C17H23N5O3: C, 59.1; H, 6.7; N, 20.3. Found: C, 59.4; H, 6.6; N, 20.3%.

Workup

  1. temperatureat reflux temperature for 4 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 (0-10%) of MeOH/DCM

Sources & evidence

ORD record
ord-2efa1c12f27c481c9943872ac756909c
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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