Methyl iodide → 4-amino-N-[3-tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenyl]-N-methylbenzamide

HRID 2390838Notes

Reaction equation

HRID 2390838 reaction equation
[C:1]([C:5]1[C:6]([O:31][CH3:32])=[C:7]([NH:19][C:20](=[O:30])[C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)[CH:8]=[C:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:36]>C1COCC1>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]([N:19]([C:7]2[CH:8]=[C:9]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:10]=[C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])[C:6]=2[O:31][CH3:32])[CH3:36])=[O:30])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67069874N-[3-tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenyl]-4-nitrobenzamide

Product 1

HCID 672926244-amino-N-[3-tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenyl]-N-methylbenzamideYield 99.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

steps 1 & 2—To a solution of 102 (0.24 g, 0.55 mmol) in THF (5 mL) was added sodium hydride (0.033 g, 0.83 mmol). The mixture was stirred at RT until the evolution of gas subsided, and iodomethane (0.069 mL, 1.1 mmol) was added. The resulting mixture was stirred for 3 h and then quenched with water and the mixture extracted with EtOAc. The solvent was evaporated, and the crude residue was dissolved in EtOAc/hexane (2:1, 10 mL) to which was added 10% Pd/C (0.025 g). A stream of hydrogen gas was bubbled through the solution for 20 min, and the resulting solution was stirred at RT for 3 h. The solution was filtered, the filtrate concentrated, and the crude residue purified by SiO2 chromatography eluting with EtOAc/hexane to afford 0.23 g (97%) of 4-amino-N-[3-tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenyl]-N-methylbenzamide (140) as a white foam.

Workup

  1. stirringThe resulting mixture was stirred for 3 h
  2. customquenched with water
  3. extractionthe mixture extracted with EtOAc
  4. customThe solvent was evaporated
  5. dissolutionthe crude residue was dissolved in EtOAc/hexane (2:1, 10 mL) to which
  6. additionwas added 10% Pd/C (0.025 g)
  7. customA stream of hydrogen gas was bubbled through the solution for 20 min
  8. stirringthe resulting solution was stirred at RT for 3 h
  9. filtrationThe solution was filtered
  10. concentrationthe filtrate concentrated
  11. customthe crude residue purified by SiO2 chromatography
  12. washeluting with EtOAc/hexane

Sources & evidence

ORD record
ord-2920a9c46030487c89cccc4c1398caf1
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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