1-benzyloxymethyl-1H-benzimidazole → 4-((1-(benzyloxymethyl)-1H-benzo[d]imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104951Notes

Reaction equation

HRID 2104951 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH2:24]([O:26][C:27]1[CH:28]=[C:29]([O:44][CH:45]([CH3:47])[CH3:46])[C:30]([F:43])=[C:31]([CH:42]=1)/[CH:32]=[N:33]/[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1)[CH3:25]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[N:33]([CH2:32][C:31]1[CH:42]=[C:27]([O:26][CH2:24][CH3:25])[CH:28]=[C:29]([O:44][CH:45]([CH3:47])[CH3:46])[C:30]=1[F:43])[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 113223751-benzyloxymethyl-1H-benzimidazoleHCID 178418339ButyllithiumHCID 178466720HCID 178466720, compound

Product 1

HCID 688137704-((1-(benzyloxymethyl)-1H-benzo[d]imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrileYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of Intermediate 10.1 (50.0 mg, 0.210 mmol) in 2 mL THF at −78° C. was added 1.6 M solution of BuLi in THF (144 μL, 0.231 mmol). The mixture was stirred at −78° C. for 15 min, then a solution of Intermediate 7.3 (69 mg, 0.210 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at −78° C. for 30 min, was allowed to warm to rt over 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 40% EtOAc/hexanes gradient) to afford 95 mg of Intermediate 10.2 as a pale yellow oil.

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperatureto warm to rt over 1 h
  3. customwas quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-3fbdc59e942440f0ba4207a869cc4fd1
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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