Sodium hydride → 5-benzyloxy-N-[(2,6-dimethoxypyridin-3-yl)methyl)-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide

HRID 218670Notes

Reaction equation

HRID 218670 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][CH2:12][CH2:13][CH:14]2[C:19]([NH:21][C:22]1[CH:23]=[N:24][C:25]([CH:28]([CH3:30])[CH3:29])=[CH:26][CH:27]=1)=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:34][C:35]1[C:36]([O:43][CH3:44])=[N:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=1>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][CH2:12][CH2:13][CH:14]2[C:19]([N:21]([CH2:34][C:35]1[C:36]([O:43][CH3:44])=[N:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=1)[C:22]1[CH:23]=[N:24][C:25]([CH:28]([CH3:30])[CH3:29])=[CH:26][CH:27]=1)=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 178542155-benzyloxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamideHCID 178543013-(Chloromethyl)-2,6-dimethoxypyridine

Product 1

HCID 595971755-benzyloxy-N-[(2,6-dimethoxypyridin-3-yl)methyl)-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamideYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

5-Benzyloxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (2.03 g) was dissolved in dimethylformamide (27 mL), and sodium hydride (0.20 g) was added under ice-cooling. The mixture was stirred at the same temperature for 30 min. A solution of 3-chloromethyl-2,6-dimethoxypyridine (0.95 g) in dimethylformamide (6 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography to give 5-benzyloxy-N-[(2,6-dimethoxypyridin-3-yl)methyl]-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (1.43 g).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 3 hr
  3. customThe reaction mixture was partitioned between water and ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-afdbee4f4adb4169b3ee6079c99f8141
Source dataset
uspto-grants-2012_06
Patent number
US08198454B2

Reaction notes

Loading…