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Cesium carbonate → 5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-trifluoromethyl-pyridin-3-yloxy)-1H-benzimidazole

HRID 13331
Notes
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Reaction equation

HRID 13331 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:18][C:19]1[CH:41]=[CH:40][CH:39]=[CH:38][C:20]=1[O:21][C:22]1[C:36]([OH:37])=[CH:35][C:25]2[NH:26][C:27]([C:29]3[CH:34]=[N:33][CH:32]=[CH:31][N:30]=3)=[N:28][C:24]=2[CH:23]=1>[Cu]=O.CN1CCCC1=O>[F:18][C:19]1[CH:41]=[CH:40][CH:39]=[CH:38][C:20]=1[O:21][C:22]1[C:36]([O:37][C:2]2[CH:7]=[N:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[CH:35][C:25]2[NH:26][C:27]([C:29]3[CH:34]=[N:33][CH:32]=[CH:31][N:30]=3)=[N:28][C:24]=2[CH:23]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 1356979845-(2-fluorophenoxy)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole

Product 1

HCID 231457785-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-trifluoromethyl-pyridin-3-yloxy)-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 14829Copper oxide
Catalyst
HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

16 mg of 5-bromo-2-trifluoromethyl-pyridine, 50 mg of cesium carbonate and 10 mg of copper(II) oxide were added to an N-methylpyrrolidinone (1 ml) solution of 21 mg of 5-(2-fluorophenoxy)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole obtained in Example 251 (step 1), and the reaction liquid was stirred at 130° C. for 5 hours. The deposit was separated through filtration, and the solution was purified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]. The resulting fraction was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure to obtain the entitled compound as a brown solid.

Workup

  1. customthe reaction liquid
  2. customThe deposit was separated through filtration
  3. customthe solution was purified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]
  4. additionThe resulting fraction was diluted with ethyl acetate
  5. washwashed with aqueous saturated sodium bicarbonate
  6. dry with materialdried with anhydrous sodium sulfate
  7. customThe solvent was evaporated away under reduced pressure

Sources & evidence

ORD record
ord-a8cabb912c264e1fb37b38fd8adc589b
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07728025B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes