4-Chlorobenzoic Acid → (2r,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide p-chlorobenzoate salt

HRID 1642366

Reaktionsgleichung

Reaktionsgleichung von HRID 1642366
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][CH:18]2[CH:23]([NH:24][C:25]([C:27]3[O:28][C:29]4[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=4[CH:31]=3)=[O:26])[CH:22]3[CH2:36][CH2:37][N:19]2[CH2:20][CH2:21]3)[CH:12]=1>CC(C)=O.C(O)(C)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][C@@H:18]2[C@H:23]([NH:24][C:25]([C:27]3[O:28][C:29]4[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=4[CH:31]=3)=[O:26])[CH:22]3[CH2:36][CH2:37][N:19]2[CH2:20][CH2:21]3)[CH:12]=1

Komponenten

5

Edukt 2

HCID 63184-Chlorobenzoic AcidHCID 22311391N-(2-(Pyridin-3-ylmethyl)quinuclidin-3-yl)benzofuran-2-carboxamide

Produkt 1

HCID 66757136(2r,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide p-chlorobenzoate saltAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittelHCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

Solid p-chlorobenzoic acid (46.8 mg, 0.299 mmol) was added in one portion to a solution of the earlier eluting isomer of N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl]benzofuran-2-carboxamide from Example 15 (108 mg, 0.299 mmol) in acetone (10 mL). This mixture was warmed to near reflux for 30 min and cooled to ambient temperature. No precipitate formed, so the solution was concentrated to about 20% of its former volume (hot plate), at which point crystals began to form. The mixture was cooled and diluted with isopropanol (2 mL). This mixture was concentrated by slow evaporation of solvent at ambient temperature, and the resulting solids were collected and dried. This produced 145 mg (94% yield) of light yellow crystals, mp 150-152° C. 1H NMR (300 MHz, CDCl3) δ 8.49 (s, 1H), 8.38 (d, 1H), 7.93 (d, 2H, p-chlorobenzoic acid), 7.67 (m, 2H), 7.57 (d, 1H), 7.45 (m, 1H), 7.36 (d, 2H, p-chlorobenzoic acid), 7.30 (m, 1H), 7.27 (s, 1H), 7.16 (m,1H), 7.00 (d, 1H, amide), 6.90 (broad s, quatemary ammonium), 4.62 (m, 1H), 3.85 (dd, 1H), 3.36 (m, 1H), 2.95-3.25 (m, 5H), 2.16 (s, 1H), 1.70-2.10 (m, 4H).

Aufarbeitung

  1. temperatureThis mixture was warmed
  2. temperatureto near reflux for 30 min
  3. customNo precipitate formed, so the solution
  4. concentrationwas concentrated to about 20% of its former volume (hot plate), at which point crystals
  5. customto form
  6. temperatureThe mixture was cooled
  7. concentrationThis mixture was concentrated by slow evaporation of solvent at ambient temperature
  8. customthe resulting solids were collected
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-45c9865bdcad4b1e8de585e66e1d147c
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08119659B2

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