Sodium hydride → HCID 67685028, compound

HRID 2400288Notes

Reaction equation

HRID 2400288 reaction equation
[CH3:1][CH:2]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[C:9]([Cl:16])[CH:8]=2)[CH2:3][CH3:4].[H-].[Na+].Cl[CH2:20][C:21]1[N:26]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>CN(C)C=O.O>[CH3:1][CH:2]([C:5]1[N:6]([CH2:20][C:21]2[N:26]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:24]=[CH:23][CH:22]=2)[C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[C:9]([Cl:16])[CH:8]=2)[CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 53404482Methyl 6-(chloromethyl)pyridine-2-carboxylateHCID 69670779HCID 69670779, compound

Product 1

HCID 67685028HCID 67685028, compoundYield 69.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(butan-2-yl)-6-chloro-5-methoxy-1H-indole (289 mg) in N,N-dimethylformamide (6.1 mL) was added sodium hydride (dispersed in liquid paraffin, 55% or more, 73 mg) under ice-cooling. This mixture was stirred for 1 hour under ice-cooling. Subsequently, methyl 6-chloromethylpyridine-2-carboxylate (271 mg) was added thereto, followed by stirring at 80° C. for 21 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous ammonium chloride solution/water (2/1, 30 mL) was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (328 mg). 1H-NMR (CDCl3) δ ppm: 0.84 (3H, t, J=7.4 Hz), 1.23 (3H, d, J=6.9 Hz), 1.45-1.80 (2H, m), 2.60-2.75 (1H, m), 3.93 (3H, s), 4.06 (3H, s), 5.50 (2H, s), 6.31 (1H, s), 6.40-6.50 (1H, m), 7.12 (1H, s), 7.15 (1H, s), 7.64 (1H, t, J=7.9 Hz), 7.95-8.05 (1H, m).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringby stirring at 80° C. for 21 hours
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine successively
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-5ddc889e24974d5198c15d9110bf40eb
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

Loading…