Methanesulfonic Acid → (2s,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide methanesulfonate salt

HRID 45292Notes

Reaction equation

HRID 45292 reaction equation
[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][C@H:13]2[C@H:18]([NH:19][C:20]([C:22]3[O:23][C:24]4[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=4[CH:26]=3)=[O:21])[CH:17]3[CH2:31][CH2:32][N:14]2[CH2:15][CH2:16]3)[CH:7]=1>C(O)C>[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][C@H:13]2[C@H:18]([NH:19][C:20]([C:22]3[O:23][C:24]4[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=4[CH:26]=3)=[O:21])[CH:17]3[CH2:31][CH2:32][N:14]2[CH2:15][CH2:16]3)[CH:7]=1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 25147644Bradanicline

Product 1

HCID 86627856(2s,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide methanesulfonate saltYield 92.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methanesulfonic acid (33.2 mg, 0.346 mmol) was added to a solution of (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide (125 mg, 0.346 mmol) in hot ethanol (1 mL). Cooling failed to produce a precipitate. The mixture was refluxed, and the hot mixture was filtered through a cotton plug, which was subsequently rinsed with methanol (1 mL). The volatiles were removed by rotary evaporation, and the residue (light yellow foam) was dissolved in hot isopropanol (1 mL). Again, cooling failed to give a precipitate. The isopropanol was evaporated, and the residue was slurried in acetone (1 mL). Filtration and vacuum oven drying (18 h at 50° C.) gave 146 mg (92.5% yield) of light beige solid, mp 240-243° C. 1H NMR (300 MHz, D2O) δ 8.32 (s, 1H), 7.82 (d, 1H), 7.66 (d, 1H), 7.57 (d, 1H), 7.38 (m, 2H), 7.20 (m, 1H), 7.12 (s, 1H), 7.01 (m, 1H), 4.09 (d, 1H), 3.75 (m, 1H), 3.47 (m, 2H), 3.00-3.40 (m, 4H), 2.67 (s, 3H, methanesulfonic acid), 1.75-2.15 (m, 5H).

Workup

  1. temperatureCooling
  2. customto produce a precipitate
  3. temperatureThe mixture was refluxed
  4. filtrationthe hot mixture was filtered through a cotton plug, which
  5. washwas subsequently rinsed with methanol (1 mL)
  6. customThe volatiles were removed by rotary evaporation
  7. dissolutionthe residue (light yellow foam) was dissolved in hot isopropanol (1 mL)
  8. temperatureAgain, cooling
  9. customto give a precipitate
  10. customThe isopropanol was evaporated
  11. filtrationFiltration and vacuum oven
  12. customdrying (18 h at 50° C.)
  13. customgave 146 mg (92.5% yield) of light beige solid, mp 240-243° C

Sources & evidence

ORD record
ord-74058dedade143f28e24cc39d858a3ec
Source dataset
uspto-grants-2013_09
Patent number
US08541446B2

Reaction notes

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