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

반응식

HRID 45294 반응식
[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

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 180Acetone용매HCID 3776Isopropanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-44a80a084dc14fe683d2fa433029e3d8
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541446B2

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