Benzene, 1-(chloromethyl)-2-fluoro- → HCID 22327407, compound

HRID 495666Notes

Reaction equation

HRID 495666 reaction equation
[CH2:1]([N:3]([CH2:22][CH3:23])[CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([C:19]#[N:20])[CH:13]=[C:14]([C:15]([F:18])([F:17])[F:16])[C:9]=2[NH:8][C:7]1=[O:21])[CH3:2].[F:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27]Cl.[C:33](=[O:36])([O-])[O-:34].[K+].[K+]>CN(C)C=O>[F:16][C:15]([F:18])([F:17])[C:33]([OH:34])=[O:36].[CH2:22]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([C:19]([NH2:20])=[O:34])[CH:13]=[C:14]([C:15]([F:16])([F:17])[F:18])[C:9]=2[N:8]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=2[F:24])[C:7]1=[O:21])[CH3:23]

Participants

5

Reactant 3

HCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 11430Potassium CarbonateHCID 22327412HCID 22327412, compound

Product 1

HCID 22327407HCID 22327407, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-[2-(diethylamino)ethyl]-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile (10.3 mg), 2-fluorobenzyl chloride (0.05 ml) and potassium carbonate (23.8 mg) in N,N-dimethylformamide (1.5 ml) was stirred with heating at 80° C. for 1.5 hours. The reaction mixture was concentrated in vacuo. To the resultant residue was added t-butanol (1.5 ml), and the mixture was stirred with heating at 60° C. To the solution was added powdered potassium hydroxide crashed in mortar (46.7 mg), and the mixture was stirred with heating at 60° C. for 1 hour. To the reaction mixture was added 1N hydrochloric acid, and the mixture was concentrated in vacuo. The resultant residue was purified by HPLC using condition 2 to give the title compound (9.1 mg, 51%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionTo the resultant residue was added t-butanol (1.5 ml)
  3. temperaturewith heating at 60° C
  4. additionTo the solution was added
  5. stirringthe mixture was stirred
  6. temperaturewith heating at 60° C. for 1 hour
  7. additionTo the reaction mixture was added 1N hydrochloric acid
  8. concentrationthe mixture was concentrated in vacuo
  9. customThe resultant residue was purified by HPLC

Sources & evidence

ORD record
ord-1cce96023881400e8d1be8030ae42b42
Source dataset
uspto-grants-2005_09
Patent number
US06939887B2

Reaction notes

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