N-(2-aminoethyl)-N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amine → N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-7-bromo phenazine-1-carboxamide

HRID 2273653Notes

Reaction equation

HRID 2273653 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]1[C:6]([CH:7]=[CH:8][CH:9]=[C:10]1[C:16]([OH:18])=O)=[N:5]2.[NH2:19][CH2:20][CH2:21][N:22]([CH2:33][CH3:34])[CH2:23][CH2:24][O:25][C:26]1[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=1>S(Cl)(Cl)=O.ClCCl>[CH2:33]([N:22]([CH2:21][CH2:20][NH:19][C:16]([C:10]1[C:11]2[C:6](=[N:5][C:4]3[C:13]([N:12]=2)=[CH:14][CH:15]=[C:2]([Br:1])[CH:3]=3)[CH:7]=[CH:8][CH:9]=1)=[O:18])[CH2:23][CH2:24][O:25][C:26]1[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=1)[CH3:34]

Participants

5

Reactant 2

HCID 45258965N-(2-aminoethyl)-N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amineHCID 592287517-Bromophenazine-1-carboxylic acid

Product 1

HCID 52952476N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-7-bromo phenazine-1-carboxamideYield 95.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 7-bromophenazine-1-carboxylic acid (81) (333 mg, 1.10 mmol) (Madelmont, J. C.; Chezal, J. M.: Moins, N.; Teulade, J. C.; Chavignon, O. Labelled analogues of halobenzamides as radiopharmaceuticals, WO 2008/012782A3) in thionyl chloride (8 mL) was refluxed, under argon, for 1 h. After cooling to room temperature, the solvent was evaporated under reduce pressure and the residue was dissolved in anhydrous toluene (5 mL). The solvent was evaporated under vacuum and the residue was dissolved in anhydrous dichloromethane (11 mL). A solution of compound 5 (300 mg, 1.32 mmol) in anhydrous dichloromethane (5 mL) was added, at 0° C. and the mixture was then stirred at room temperature for 24 h. The solvent was evaporated under reduce pressure and the residue was chromatographed (Al2O3, AcOEt) to give compound 82 (537 mg, 1.05 mmol) as a yellow oil. Yield 95%; Rf (Al2O3, AcOEt) 0.69; IR (CCl4) ν 1190, 1249, 1283, 1466, 1517, 1663, 2800-3000, 3250-3350 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.09 (t, 3H, J=7.1 Hz), 2.80 (q, 2H, J=7.1 Hz), 2.86 (t, 2H, J=6.0 Hz), 3.00 (t, 2H, J=5.5 Hz), 3.70 (q, 2H, J=6.0 Hz), 4.04 (t, 2H, J=5.5 Hz), 6.75 (ddd, 1H, 5JH-F=0.8 Hz, J=4.8, 7.9 Hz), 6.93 (ddd, 1H, 4JH-F=10.1 Hz, J=1.5, 7.9 Hz), 7.45 (td, 1H, 4JH-F=1.5 Hz, J=1.5, 4.8 Hz), 7.71 (dd, 1H, J=2.0, 9.2 Hz), 7.82 (dd, 1H, J=7.1, 8.7 Hz), 7.89 (d, 1H, J=9.2 Hz), 8.15 (dd, 1H, J=1.5, 8.7 Hz), 8.23 (d, 1H, J=2.0 Hz), 8.84 (dd, 1H, J=1.5, 7.1 Hz), 10.79 (m, 1H); ESI-MS m/z 512.0 [M+H]+.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe residue was dissolved in anhydrous toluene (5 mL)
  3. customThe solvent was evaporated under vacuum
  4. dissolutionthe residue was dissolved in anhydrous dichloromethane (11 mL)
  5. customThe solvent was evaporated
  6. customthe residue was chromatographed (Al2O3, AcOEt)

Sources & evidence

ORD record
ord-f71d8a5c720c452db0754762066a94ea
Source dataset
uspto-grants-2015_09
Patent number
US09125937B2

Reaction notes

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