Sodium hydride → 3-[1-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-1H-imidazol-4-yl]-pyridine

HRID 1632049Notes

Reaction equation

HRID 1632049 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1.[H-].[Na+].Br[CH2:15][C:16]1[C:17]([F:31])=[C:18]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=2)[C:19]([O:22][CH3:23])=[CH:20][CH:21]=1>C1COCC1>[Cl:30][C:26]1[CH:25]=[C:24]([C:18]2[C:19]([O:22][CH3:23])=[CH:20][CH:21]=[C:16]([CH2:15][N:1]3[CH:5]=[C:4]([C:6]4[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=4)[N:3]=[CH:2]3)[C:17]=2[F:31])[CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 577037013-Bromomethyl-3'-chloro-2-fluoro-6-methoxy-biphenylHCID 178420772HCID 178420772, compound

Product 1

HCID 580202303-[1-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-1H-imidazol-4-yl]-pyridineYield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A flask was charged with 3-(1H-Imidazol-4-yl)-pyridine (165 mg, 0.75 mmol) and THF (5 mL). Then NaH (60% dispersion in mineral oil, 60 mg, 1.5 mmol) was added slowly (gas evolution). After 2 min. of stirring at room temperature 3-Bromomethyl-3′-chloro-2-fluoro-6-methoxy-biphenyl (165 mg, 0.5 mmol) was added. The reaction mixture was stirred at rt. After overnight stirring the reaction mixture was quenched with water (20 mL). The mixture was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated in-vacuo. The crude was purified by silica gel column chromatography, eluted with dichloromethane/MeOH (200:5) to produce 77.1 mg (39% yield) of the product (P-479) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d) δ 3.75 (s, 3H), 5.26 (s, 2H), 7.02 (d, J=, 8.59 Hz, 1H), 7.28-7.50 (m, 6H), 7.78-7.88 (m, 2H), 8.04-8.11 (m, 1H), 8.38 (dd, J=4.7, 1.2 Hz, 1H), 8.96 (d, J=1.5 Hz, 1H) ppm.

Workup

  1. additionwas added
  2. stirringAfter overnight stirring the reaction mixture
  3. customwas quenched with water (20 mL)
  4. extractionThe mixture was extracted with EtOAc (3×10 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in-vacuo
  8. customThe crude was purified by silica gel column chromatography
  9. washeluted with dichloromethane/MeOH (200:5)

Sources & evidence

ORD record
ord-1ee0f5a69d254f569be2210404b5ce96
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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