Cesium carbonate → 4-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carbonitrile

HRID 922753Notes

Reaction equation

HRID 922753 reaction equation
Br[CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:8][C:9]([C:13]#[N:14])=[N:10]2)=[CH:5][CH:4]=1.[CH3:22][N:23]1[CH2:27][C:26](=[O:28])[NH:25][C:24]1=[O:29].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:7]2[C:6]3[C:11](=[CH:12][C:3]([CH2:2][N:25]4[C:26](=[O:28])[CH2:27][N:23]([CH3:22])[C:24]4=[O:29])=[CH:4][CH:5]=3)[N:10]=[C:9]([C:13]#[N:14])[CH:8]=2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 692171-MethylhydantoinHCID 194270117-(Bromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile

Product 1

HCID 715655234-(4-Fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carbonitrileYield 87.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-(Bromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile (2-1, 50.0 mg, 0.147 mmol, 1.0 equiv.), 1-methylimidazolidine-2,4-dione (18.4 mg, 0.161 mmol, 1.1 equiv.) and cesium carbonate (95.0 mg, 0.293 mmol, 2.0 equiv.) were combined into 1.0 ml of DMF. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was filtered and the filtrate was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(4-fluorophenyl)-7-[(3-methyl-2,5-dioxoimidazolidin-1-yl)methyl]quinoline-2-carbonitrile (2-2, 48.0 mg, 87.0%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.205 (d, J=1.09 Hz, 1H); 7.941 (d, J=8.79 Hz, 1H); 7.681 (dd, J1=8.79 Hz, JZ=1.83 Hz, 1H); 7.647 (s, 1H); 7.454-7.503 (m, 2H); 7.251-7.309 (m, 2H); 4.935 (s, 2H); 4.049 (s, 2H); 3.057 (s, 3H). LRMS m/z (M+H)+ 375.1 found, 375.1 required.

Workup

  1. filtrationThe solid was filtered
  2. customthe filtrate was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-6aef84e3013743639783b7e99ccb234d
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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