Sodium hydride → HCID 71117584, compound

HRID 2368539Notes

Reaction equation

HRID 2368539 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([CH:15]([OH:17])[CH3:16])=[C:13]([CH3:18])[N:12]=[C:11]2[S:19][CH2:20][C:21]2[C:26]([F:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=2[F:29])=[CH:6][CH:5]=1.Br.Br[CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1>C1COCC1>[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([CH:15]([O:17][CH2:32][C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)[CH3:16])=[C:13]([CH3:18])[N:12]=[C:11]2[S:19][CH2:20][C:21]2[C:26]([F:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=2[F:29])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 127522194-(Bromomethyl)pyridine hbrHCID 71117585HCID 71117585, compound

Product 1

HCID 71117584HCID 71117584, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% in mineral oil, 60 mg, 1.44 mmol) was added to a solution of 1-(1-(4-fluorophenyl)-4-methyl-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazol-5-yl)ethanol (62) (190 mg, 0.48 mmol) in THF (5 mL) and the reaction was allowed to stir at room temperature for 20 min. 4-(bromomethyl)pyridine hydrobromide (146 mg, 0.576 mmol) was added to the reaction mixture and heated to 70° C. overnight. The reaction was cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes) to afford 4-((1-(1-(4-fluorophenyl)-4-methyl-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazol-5-yl)ethoxy)methyl)pyridine (628). 1H NMR (400 MHz, CDCl3) δ: 8.56 (d, J=6.0, 2H), 7.20-7.17 (m, 4H), 7.04-6.96 (m, 3H), 6.74-6.68 (m, 1H), 5.31-5.15 (m, 2H), 4.63 (q, J=6.4, 1H), 4.48 (d, J=13.5, 1H), 4.32 (d, J=13.5, 1H), 2.19 (s, 3H), 1.45 (d, J=6.4, 3H). LC-MS ESI m/z; found 488.2 [M+H]+.

Workup

  1. temperatureheated to 70° C. overnight
  2. temperatureThe reaction was cooled to room temperature
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-939484dfe64e4d9e824d33fbb2acaf3c
Source dataset
uspto-grants-2014_04
Patent number
US08703776B2

Reaction notes

Loading…