Dimethylformamide → 2-((5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione

HRID 216874Notes

Reaction equation

HRID 216874 reaction equation
Br[CH2:2][C:3]1[C:12]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[Cl:20])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[Cl:21])[N:4]=1.CN(C=O)C.[C:27]1(=[O:37])[NH:31][C:30](=[O:32])[C:29]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:28]12.[K]>>[Cl:21][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:11]=[C:12]([C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[Cl:20])[C:3]([CH2:2][N:31]1[C:27](=[O:37])[C:28]3[C:29](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:30]1=[O:32])=[N:4]2

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24194345Phthalimide potassium saltHCID 577078212-(Bromomethyl)-5-chloro-3-(2-chloro-5-fluorophenyl)quinoxaline

Product 1

HCID 577078152-((5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione

Conditions

Temperature
100 °C

Procedure

To a heterogeneous mixture of 2-(bromomethyl)-5-chloro-3-(2-chloro-5-fluoro-phenyl)quinoxaline (0.1815 g, 0.4702 mmol) in DMF (3.444 mL, 0.4702 mmol) was added potassium phthalimide (0.2177 g, 1.175 mmol) and the heterogeneous mixture was stirred at 100° C. After stirring at 100° C. for 30 min, the mixture was concentrated under reduced pressure and triturated with water (30 mL). The precipitate was collected by filtration. The resulting solid was filtered and washed with 2 N NaOH (30 mL) and then with water (100 mL), and air-dried to give 2-((5-chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (1H, dd, J=7.6, 1.4 Hz), 7.95-8.01 (1H, m), 7.82-7.91 (5H, m), 7.65-7.75 (2H, m), 7.43-7.52 (1H, m), 4.99 (2H, br. s.); LC-MS (ESI) m/z 452.0 [M+H]+. The crude product was carried on crude without purification for the next step.

Workup

  1. stirringAfter stirring at 100° C. for 30 min
  2. concentrationthe mixture was concentrated under reduced pressure
  3. customtriturated with water (30 mL)
  4. filtrationThe precipitate was collected by filtration
  5. filtrationThe resulting solid was filtered
  6. washwashed with 2 N NaOH (30 mL)
  7. dry with materialwith water (100 mL), and air-dried

Sources & evidence

ORD record
ord-c4bea37a969a4c3d8bb2ecbf291e7dec
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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