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Cesium carbonate → 2-{1-[2-fluoro-5-(trifluoromethyl)benzyl]-3-methyl-2-oxo-2,3-dihydro 1H-imidazo[4,5-b]pyridin-5-yl}benzonitrile

HRID 1616215
Notes
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Reaction equation

HRID 1616215 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[CH:9][CH:10]=[C:5]2[NH:4][C:3]1=[O:19].C(=O)([O-])[O-].[Cs+].[Cs+].[F:26][C:27]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:28]=1[CH2:29]Br>CN1C(=O)CCC1.CO>[F:26][C:27]1[CH:34]=[CH:33][C:32]([C:35]([F:36])([F:37])[F:38])=[CH:31][C:28]=1[CH2:29][N:4]1[C:5]2[C:6](=[N:7][C:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[CH:9][CH:10]=2)[N:2]([CH3:1])[C:3]1=[O:19]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27375712-(Bromomethyl)-1-fluoro-4-(trifluoromethyl)benzeneHCID 866918212-(3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)benzonitrile

Product 1

HCID 866918222-{1-[2-fluoro-5-(trifluoromethyl)benzyl]-3-methyl-2-oxo-2,3-dihydro 1H-imidazo[4,5-b]pyridin-5-yl}benzonitrile

Reagents, catalysts & solvents 2

HCID 887
Methanol
Solvent
HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

2-(3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)benzonitrile (4-1) (30 mg, 0.12 mmol) and cesium carbonate (117 mg, 0.36 mmol) were added to a microwave vial and suspended in NMP (0.5 mL) under nitrogen. 2-Fluoro-5-(trifluoromethyl)benzyl bromide (47 mg, 0.18 mmol) was added to the suspension and then heated at 90° C. overnight. The mixture was diluted with methanol and purified using reverse phase chromatography (10-100%, 0.1% TFA in H2O/Acetonitrile); the desired fractions were collected and concentrated to produce 2-{1-[2-fluoro-5-(trifluoromethyl)benzyl]-3-methyl-2-oxo-2,3-dihydro 1H-imidazo[4,5-b]pyridin-5-yl}benzonitrile (6-1). HRMS (M+H)+: observed=427.1179, calculated=427.1177.

Workup

  1. custompurified
  2. customthe desired fractions were collected
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-631614dee35b43ec91eb1516fe45e572
Source dataset
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08765784B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes