Methyl iodide → HCID 86685971, compound

HRID 2277677Notes

Reaction equation

HRID 2277677 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH2:19][OH:20])[CH:18]=1)[CH2:6][CH2:5]2.[H-].[Na+].[H][H].[CH3:25]I>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH2:19][O:20][CH3:25])[CH:18]=1)[CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86685959HCID 86685959, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86685971HCID 86685971, compoundYield 14.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-chloro-2-(5-hydroxymethyl-pyridin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (example 3) (28.8 mg, 0.1 mmol) in THF (5 mL) was added NaH (8 mg, 0.2 mmol, 60% dispersion in mineral oil) at room temperature. After hydrogen evolution ceased, a solution of methyliodide (0.2 mmol) in THF (5 mL) was added dropwise, and the resulting mixture was stirred at room temperature for 1 hour. The mixture was then treated with satd. aqueous NH4Cl solution and extracted three times with EtOAc. The combined organic layer was washed with water and brine, dried over anhy. Na2SO4 and concentrated in vacuo. The crude product was purified by prep-HPLC to give the title compound (4.5 mg, 14.8%) as a white solid. MS: (M+H)+ 303.1

Workup

  1. additionThe mixture was then treated with satd
  2. extractionaqueous NH4Cl solution and extracted three times with EtOAc
  3. washThe combined organic layer was washed with water and brine
  4. customdried over anhy
  5. concentrationNa2SO4 and concentrated in vacuo
  6. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-ea7a7f75269d47408d28d7d2bf8d0b60
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

Loading…