N,N'-Dimethylethylenediamine → 1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-5-(2-oxopyrrolidin-1-yl)pyridin-2(1H)-one

HRID 1878715Notes

Reaction equation

HRID 1878715 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[CH:7]=1.CNCCNC.[NH:30]1[CH2:34][CH2:33][CH2:32][C:31]1=[O:35].C(=O)([O-])[O-].[Cs+].[Cs+].[NH4+].[OH-]>[Cu]I.C1(C)C=CC=CC=1>[CH3:22][O:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][CH2:9][CH2:8][N:6]3[CH:7]=[C:2]([N:30]4[CH2:34][CH2:33][CH2:32][C:31]4=[O:35])[CH:3]=[CH:4][C:5]3=[O:23])=[CH:12][CH:13]=[N:14]2)=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 14923Ammonium HydroxideHCID 248844955-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

Product 1

HCID 250191681-(2-(7-methoxyquinolin-4-yloxy)ethyl)-5-(2-oxopyrrolidin-1-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A dry 5 mL, 1-neck round bottom flask was charged with 5-bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one (0.0476 g, 0.13 mmol), copper(I)iodide (0.0033 mL, 0.098 mmol), 1 mL toluene, N,N′-dimethylethylenediamine (0.017 g, 0.20 mmol), 2-pyrrolidone (0.048 mL, 0.63 mmol), cesium carbonate (0.12 g, 0.38 mmol), a stirbar and a reflux condenser. The solution was placed in a 120° C. bath for 6 h. The solution was cooled and retreated with the same amounts of CuI and diamine. The solution was heated to 120° C. for 16 h, and cooled. The solution was treated with 2 mL 50% concentrated NH4OH, and stirred/sonicated for 2 min. The biphasic solution was loaded onto an unbuffered Varian Chem elute (10 mL, PN 12198007). The column was extracted with CH2Cl2 (5×10 mL), and the extracts were concentrated in vacuo. The residue was taken up in 0.5 mL 20% THF in DCE, and filtered. The solid was washed with 20% THF in DCE (2×0.5 mL). The solid was heated into 2 mL EtOH and filtered hot. The solvent was removed in vacuo to afford 1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-5-(2-oxopyrrolidin-1-yl)pyridin-2(1H)-one. 1H NMR (400 MHz, CDCl3) δ ppm 2.11-2.20 (m, 2H) 2.58 (t, J=8.12 Hz, 2H) 3.66 (t, J=6.94 Hz, 2H) 3.93 (s, 3H) 4.47-4.55 (m, 4H) 6.60 (dd, J=9.78, 0.59 Hz, 1H) 6.62 (d, J=5.38 Hz, 1H) 7.13 (dd, J=9.15, 2.59 Hz, 1H) 7.35 (d, J=2.54 Hz, 1H) 7.47 (dd, J=9.78, 2.93 Hz, 1H) 8.10 (d, J=9.10 Hz, 1H) 8.19 (dd, J=2.93, 0.59 Hz, 1H) 8.64 (d, J=5.28 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ ppm 17.91 (s, 1 C) 31.78 (s, 1 C) 48.39 (s, 1 C) 49.78 (s, 1 C) 55.46 (s, 1 C) 65.70 (s, 1 C) 99.42 (s, 1 C) 107.20 (s, 1 C) 115.69 (s, 1 C) 118.46 (s, 1C) 120.67 (s, 2 C) 123.03 (s, 1 C) 131.19 (s, 1 C) 134.70 (s, 1 C) 151.21 (s, 1 C) 151.76 (s, 1 C) 160.57 (s, 1 C) 160.79 (s, 1 C) 160.99 (s, 1 C) 173.95 (s, 1 C). MS (ESI pos. ion) m/z (MH+): 380.2, calcd for C21H21N3O4+H+=380.2.

Workup

  1. customwas placed in a 120° C.
  2. customfor 6 h
  3. temperatureThe solution was cooled
  4. temperaturecooled
  5. customstirred/sonicated for 2 min
  6. washelute (10 mL, PN 12198007)
  7. extractionThe column was extracted with CH2Cl2 (5×10 mL)
  8. concentrationthe extracts were concentrated in vacuo
  9. filtrationfiltered
  10. washThe solid was washed with 20% THF in DCE (2×0.5 mL)
  11. temperatureThe solid was heated into 2 mL EtOH
  12. filtrationfiltered hot
  13. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-35ad31f546db48d9a4344de824e7ca0b
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

Loading…