N-(3-Aminopropyl)morpholine → HCID 25139752, compound

HRID 1669148Notes

Reaction equation

HRID 1669148 reaction equation
Cl[C:2]1[N:3]=[N+:4]([O-:15])[C:5]2[CH:11]=[C:10]3[O:12][CH2:13][CH2:14][C:9]3=[CH:8][C:6]=2[N:7]=1.[N:16]1([CH2:22][CH2:23][CH2:24][NH2:25])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1>COCCOC>[N:16]1([CH2:22][CH2:23][CH2:24][NH:25][C:2]2[N:3]=[N+:4]([O-:15])[C:5]3[CH:11]=[C:10]4[O:12][CH2:13][CH2:14][C:9]4=[CH:8][C:6]=3[N:7]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 61055N-(3-Aminopropyl)morpholineHCID 25139751HCID 25139751, compound

Product 1

HCID 25139752HCID 25139752, compoundYield 85.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of chloride 196 (850 mg, 3.8 mmol) and 3-(4-morpholinyl)propylamine (1.7 mL, 11.5 mmol) in DME (30 mL) was stirred at reflux temperature for 18 h. The solution was cooled, the solvent evaporated and the residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (2×25 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (2-10%) of MeOH/DCM, to give 1-oxide 199 (1.08 g, 85%) as a yellow solid: mp 142-144° C.; 1H NMR δ 7.52 (s, 1H, H-9), 7.41 (s, 1H, H-5), 5.97 (br s, 1H, NH), 4.67 (t, J=8.3 Hz, 2H, H-7), 3.75 (t, J=4.7 Hz, 4H, 2×CH2O), 3.56 (dt, J=6.4, 5.9 Hz, 2H, CH2N), 3.35 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.42-2.53 (m, 6H, 2×CH2N, CH2), 1.83 (p, J=6.5 Hz, 2H, CH2); 13C NMR δ 158.3, 151.4, 146.1, 140.5, 128.7, 121.8, 96.7, 71.9, 67.0 (2), 57.3, 53.8 (2), 40.8, 29.7, 25.4; MS (APCI) m/z 332 (MH+, 100%). Anal. calcd for C16H21N5O3: C, 58.0; H, 6.4; N, 21.1. Found: C, 58.0; H, 6.0; N, 21.2%.

Workup

  1. temperatureat reflux temperature for 18 h
  2. temperatureThe solution was cooled
  3. customthe solvent evaporated
  4. customthe residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL)
  5. extractionThe aqueous layer was extracted with DCM (2×25 mL)
  6. customthe combined organic fraction dried
  7. customthe solvent evaporated
  8. customThe residue was purified by chromatography
  9. washeluting with a gradient (2-10%) of MeOH/DCM

Sources & evidence

ORD record
ord-b52f2a0f9212469c911d779d7ff0ad15
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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