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 45294

反応式

HRID 45294 の反応式
[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

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 3776Isopropanol溶媒

実験手順

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, quaternary 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).

後処理

  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

出典と根拠

ORDレコード
ord-44a80a084dc14fe683d2fa433029e3d8
出典データセット
uspto-grants-2013_09
特許番号
US08541446B2

関連ノート

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