Thioanisole → N-[(2,6-dimethoxypyridin-3-yl)methyl]-5-hydroxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide

HRID 2265440Notes

Reaction equation

HRID 2265440 reaction equation
C([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]([CH2:31][C:32]1[C:33]([O:40][CH3:41])=[N:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=1)[C:22]1[CH:23]=[N:24][C:25]([CH:28]([CH3:30])[CH3:29])=[CH:26][CH:27]=1)=[O:20])C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>FC(F)(F)C(O)=O>[CH3:41][O:40][C:33]1[C:32]([CH2:31][N:21]([C:22]2[CH:23]=[N:24][C:25]([CH:28]([CH3:30])[CH3:29])=[CH:26][CH:27]=2)[C:19]([CH:14]2[C:15]3[C:10](=[C:9]([OH:8])[CH:18]=[CH:17][CH:16]=3)[CH2:11][CH2:12][CH2:13]2)=[O:20])=[CH:37][CH:36]=[C:35]([O:38][CH3:39])[N:34]=1

Participants

5

Reactant 3

HCID 7520ThioanisoleHCID 516892Sodium BicarbonateHCID 595971755-benzyloxy-N-[(2,6-dimethoxypyridin-3-yl)methyl)-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide

Product 1

HCID 59597203N-[(2,6-dimethoxypyridin-3-yl)methyl]-5-hydroxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamideYield 51.8%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 5-benzyloxy-N-[(2,6-dimethoxypyridin-3-yl)methyl]-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.83 g) in trifluoroacetic acid (2.4 mL) was added thioanisole (0.49 mL), and the mixture was stirred at room temperature for one day. The reaction mixture was poured into saturated aqueous sodium hydrogencarbonate and partitioned with 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 N-[(2,6-dimethoxypyridin-3-yl)methyl]-5-hydroxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.36 g).

Workup

  1. custompartitioned with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0b97ced96b20414f8c27e621e87719cd
Source dataset
uspto-grants-2010_12
Patent number
US07855297B2

Reaction notes

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