Hydrochloric Acid → HCID 46216064, compound

HRID 410155Notes

Reaction equation

HRID 410155 reaction equation
[C:1]1([NH2:8])[C:2]([NH2:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.[CH:9](OCC)(OCC)OCC.C1(S(O)(=O)=O)C=CC=CC=1.[F:29][C:30]([F:50])([F:49])[C:31]1[C:32]([O:37][C:38]2[CH:48]=[CH:47][C:41]([C:42]([O:44]CC)=O)=[CH:40][CH:39]=2)=[N:33][CH:34]=[CH:35][CH:36]=1.[Li+].CC([N-]C(C)C)C.Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C(OCC)(=O)C>[NH:7]1[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[N:8]=[C:9]1[C:42]([C:41]1[CH:40]=[CH:39][C:38]([O:37][C:32]2[C:31]([C:30]([F:29])([F:49])[F:50])=[CH:36][CH:35]=[CH:34][N:33]=2)=[CH:48][CH:47]=1)=[O:44]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 7243O-PhenylenediamineHCID 7371Benzenesulfonic AcidHCID 14798Sodium HydroxideHCID 31214Ethyl orthoformateHCID 2724682Lithium diisopropylamideHCID 59326875Ethyl 4-(3-(trifluoromethyl)pyridin-2-yloxy)benzoate

Product 1

HCID 46216064HCID 46216064, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of benzene-1,2-diamine (175 mg, 1618 μmol), triethyl orthoformate (665 μL, 4353 μmol), and benzenesulfonic acid (10 mg, 65 μmol) in toluene (1.6 mL) was heated to reflux for 4 h and then slowly distilled to remove half of the solvent. The mixture was then cooled to RT and neutralized with diisopropyl amine, followed by addition of a solution of ethyl 4-(3-(trifluoromethyl)pyridin-2-yloxy)benzoate (554 mg, 1780 μmol) in 1.7 mL of THF. The mixture was cooled to −78° C. and 1.2 equiv of LDA (0.971 mL, 2.0M) was added. After aging at −78° C. for 1.5 h, the mixture was warmed to RT and stirred for 1.5 h and then 2N HCl was added and the mixture was agitated for 15 min. Following that, the mixture was adjusted to pH 9 with 1N NaOH. Ethyl acetate was added and the layers were separated, the aqueous was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Following purification, (1H-benzo[d]imidazol-2-yl)(4-(3-(trifluoromethyl)pyridin-2-yloxy)phenyl)methanone was obtained. MS (ESI, pos. ion) m/z: 384 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureto reflux for 4 h
  2. distillationslowly distilled
  3. customto remove half of the solvent
  4. temperatureThe mixture was cooled to −78° C.
  5. temperaturethe mixture was warmed to RT
  6. stirringthe mixture was agitated for 15 min
  7. customthe layers were separated
  8. extractionthe aqueous was extracted with ethyl acetate (3×)
  9. washthe combined organics were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurification

Sources & evidence

ORD record
ord-5dbed1a65bc24b8eb7ce41fdbd2c59e3
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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