Imidazole → HCID 86685970, compound

HRID 2277676Notes

Reaction equation

HRID 2277676 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([C:20]1[CH:21]=[N:22][CH:23]=[C:24]([CH2:26]Cl)[CH:25]=1)[CH2:13][CH2:12]2.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([C:20]1[CH:21]=[N:22][CH:23]=[C:24]([CH2:26][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)[CH:25]=1)[CH2:13][CH2:12]2

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 24758Sodium hydrideHCID 86685969HCID 86685969, compound

Product 1

HCID 86685970HCID 86685970, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
3.5 °C

Procedure

To a solution of 1H-imidazole (50 mg, 0.73 mmol) dissolved in DMF (5.0 mL) was added NaH (60% dispersion in mineral oil, 25 mg, 0.63 mmol) at 0° C. The reaction mixture was stirred at 2-5° C. for 0.5 h before 6-chloro-2-(5-chloromethyl-pyridin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (example 140 [A]) (85 mg, 0.28 mmol) was added. The mixture was then stirred at 2-5° C. for additional 2 hours before it was warmed up to room temperature and poured into water (5.0 mL). After extraction with EtOAc (2×50 mL), the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was purified by prep-HPLC to give the title compound (30 mg, 31%) as a white foam. MS: 339.2 (M+H+).

Workup

  1. additionwas added
  2. temperaturewas warmed up to room temperature
  3. extractionAfter extraction with EtOAc (2×50 mL)
  4. washthe organic layer was washed with brine
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo
  8. customto give a crude product which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-d980b30c2cee45a8b713c35aa4e69dc4
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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