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

HRID 45290Notes

Reaction equation

HRID 45290 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][C@H:16]2[C@H:21]([NH:22][C:23]([C:25]3[O:26][C:27]4[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=4[CH:29]=3)=[O:24])[CH:20]3[CH2:34][CH2:35][N:17]2[CH2:18][CH2:19]3)[CH:10]=1.C(O)(C)C>C(OC(C)C)(=O)C>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][C@H:16]2[C@H:21]([NH:22][C:23]([C:25]3[O:26][C:27]4[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=4[CH:29]=3)=[O:24])[CH:20]3[CH2:34][CH2:35][N:17]2[CH2:18][CH2:19]3)[CH:10]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 444266Maleic Acid2×HCID 25147644Bradanicline

Product 1

HCID 66787380(2s,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide maleate saltYield 84.7%

Reagents, catalysts & solvents 1

HCID 7915Isopropyl AcetateSolvent2×

Procedure

Maleic acid (0.067 g, 0.630 mmol) was added to a hot slurry of (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide (0.203 g, 0.560 mmol) in isopropyl acetate (2 mL), depositing fine, white solids, along with a gummy residue. Additional isopropyl acetate (3 mL) and maleic acid (0.006 g) were added, and the mixture was heated to reflux. Isopropanol (5 mL) was added at reflux. The resulting mixture of white solids was cooled to ambient temperature, filtered, and the solids were washed with isopropyl acetate (2 mL). The product was dried under vacuum at 60° C. for 18 h to give 0.228 g of an off-white, flaky solid (84.7% yield), mp 180-182° C. 1H NMR (DMSO-d6) indicated a mono-salt stoichiometry. Calc'd for C22H23N3O2 C4H4O4: C, 65.40; H, 5.70; N, 8.80. Found: C, 65.35, 65.29; H, 5.86, 5.68; N, 8.69, 8.78.

Workup

  1. temperaturethe mixture was heated to reflux
  2. temperatureat reflux
  3. additionThe resulting mixture of white solids
  4. filtrationfiltered
  5. washthe solids were washed with isopropyl acetate (2 mL)
  6. customThe product was dried under vacuum at 60° C. for 18 h

Sources & evidence

ORD record
ord-47b4fbe64b534ec6b2d806960906b9c8
Source dataset
uspto-grants-2013_09
Patent number
US08541446B2

Reaction notes

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