1-(benzyloxymethyl)-2-phenyl-1H-imidazole → 4-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104956Notes

Reaction equation

HRID 2104956 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]C(CC)C.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]([F:45])=[C:33]([CH:44]=1)/[CH:34]=[N:35]/[C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1)[CH3:27]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([N:35]([CH2:34][C:33]2[CH:44]=[C:29]([O:28][CH2:26][CH3:27])[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]=2[F:45])[C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 578039651-(benzyloxymethyl)-2-phenyl-1H-imidazoleHCID 178418400CID 53628100HCID 178466720HCID 178466720, compound

Product 1

HCID 688133704-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrileYield 24.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of Intermediate 15.1 (100 mg, 0.378 mmol) in 2 mL THF at 0° C., was added sec-BuLi (0.81 M in cyclohexane, 514 μL, 0.416 mmol). The mixture was stirred at 0° C. for 10 min, then a solution of Intermediate 7.3 (123 mg, 0.378 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at 0° C. for 30 min and rt 1 h, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient) followed by preparative HPLC purification to afford 53.7 mg of Intermediate 15.2.

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 min and rt 1 h
  2. customwas quenched with sat. NH4Cl
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient)
  8. customfollowed by preparative HPLC purification

Sources & evidence

ORD record
ord-f2d3969455624f90b068529c099f105f
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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