p,p'-Dimethoxybenzhydryl alcohol → N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide

HRID 1504760Notes

Reaction equation

HRID 1504760 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[N:13]=2)[C:5]([C:8]([NH2:10])=[O:9])=[N:6][CH:7]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)O)=[CH:24][CH:23]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:37][O:36][C:33]1[CH:32]=[CH:31][C:30]([CH:28]([C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)[NH:10][C:8]([C:5]2[C:4]([NH:11][C:12]3[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[N:13]=3)=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)=[O:9])=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 69768p,p'-Dimethoxybenzhydryl alcoholHCID 521998p-Toluenesulfonic acid monohydrateHCID 867316575-Bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide

Product 1

HCID 86731658N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide (1.65 g, 5.14 mmol) in toluene (20 ml) was added bis(4-methoxyphenyl)methanol (1.32 g, 5.39 mmol) and p-toluenesulfonic acid monohydrate (0.098 g, 0.51 mmol). The reaction mixture was heated to reflux with a Dean-Stark apparatus attached. After 2 hours, the reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (600 mL). This mixture was washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (50 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes). The isolated product was dissolved in 25 mL hot ethyl acetate (˜50° C.). The mixture was allowed to cool to ambient temperature, and then it was diluted dropwise with hexanes (100 mL). After 4 hours, the mixture was filtered, and the collected solids were dried under reduced pressure to afford N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide. MS ESI calc'd. For C28H28BrN4O3 [M+H]+ 547 and 549. found 547 and 549. 1H NMR (500 MHz, DMSO-d6) δ 11.47 (s, 1H), 9.68 (d, J=2.0 Hz, 1H), 9.26 (d, J=8.5 Hz, 1H), 8.18 (d, J=2.0 Hz, 1H), 7.27 (d, J=8.5 Hz, 4H), 6.88 (d, J=8.5 Hz, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 6.19 (d, J=9.0 Hz, 1H), 3.71 (s, 6H), 2.36 (s, 3H), 2.19 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux with a Dean-Stark apparatus
  3. washThis mixture was washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (50 mL)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes)
  8. dissolutionThe isolated product was dissolved in 25 mL hot ethyl acetate (˜50° C.)
  9. temperatureto cool to ambient temperature
  10. additionit was diluted dropwise with hexanes (100 mL)
  11. waitAfter 4 hours
  12. filtrationthe mixture was filtered
  13. customthe collected solids were dried under reduced pressure

Sources & evidence

ORD record
ord-087abb1dd20043b3a99856124bcd1c83
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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