Benzimidazole → 7-((1H-Benzo[d]imidazol-1-yl)methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide

HRID 922760Notes

Reaction equation

HRID 922760 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[CH:14][C:15]([C:19]([NH2:21])=[O:20])=[N:16]2)=[CH:11][CH:10]=1.[N:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[NH:31][CH:30]=1>CN(C=O)C>[N:29]1([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)=[CH:14][C:15]([C:19]([NH2:21])=[O:20])=[N:16]3)=[CH:11][CH:10]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[CH:30]1

Participants

5

Reactant 3

HCID 5798BenzimidazoleHCID 10796Cesium carbonateHCID 895440027-(Bromomethyl)-4-(4-fluorophenyl)-2-quinolinecarboxamide

Product 1

HCID 715662787-((1H-Benzo[d]imidazol-1-yl)methyl)-4-(4-fluorophenyl)quinoline-2-carboxamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cs2CO3 (91 mg, 0.278 mmol, 2.0 equiv.) was added to a solution of 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-1, 50 mg, 0.139 mmol, 1.0 equiv.) and benzimidazole (18.09 mg, 0.153 mmol, 1.1 equiv.) in DMF (696 μl) and the reaction stirred at rt for 2 hours. The crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier). A Waters Porapak® Rxn CX (6 cc) was conditioned with MeOH (5 mL). Fractions containing the desired product were loaded onto the cartridge and the cartridge was washed with MeOH (10 mL). The desired product was eluted with 2M NH3 in MeOH (5 mL) and the solvent removed in vacuo to afford 7-((1H-Benzo[d]imidazol-1-yl)methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-2, 23.6 mg, 43%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.40 (s, 1H); 8.09 (s, 1H); 8.00-7.91 (m, 2H); 7.73-7.70 (m, 1H); 7.61-7.55 (m, 3H); 7.47 (dd, J=7.2, 2.0 Hz, 1H); 7.33-7.23 (m, 4H); 5.80 (s, 2H). LRMS m/z (M+H)+ 397.17 found, 397.42 required.

Workup

  1. customThe crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)
  2. additionFractions containing the desired product
  3. washthe cartridge was washed with MeOH (10 mL)
  4. washThe desired product was eluted with 2M NH3 in MeOH (5 mL)
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-327c6017744f4eeba9526e0407e59ab2
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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