Potassium Carbonate → 7-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

HRID 273224

反応式

HRID 273224 の反応式
CC1C=CC(S(O[CH2:12][CH2:13][C:14]2[N:15]=[CH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[C:19]([Br:24])[CH:18]=3)(=O)=O)=CC=1.[CH3:25][C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:24][C:19]1[CH:18]=[C:17]2[C:22]([CH:23]=[C:14]([CH2:13][CH2:12][N:27]3[CH2:28][CH2:29][CH2:30][C@H:26]3[CH3:25])[N:15]=[CH:16]2)=[CH:21][CH:20]=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 641544(R)-2-MethylpyrrolidineHCID 865922262-(7-Bromo-3-isoquinolinyl)ethyl 4-methylbenzenesulfonate

生成物 1

HCID 671046927-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
52.5 °C

実験手順

The product from Example 52F was dissolved in a solution of (2R)-2-methylpyrrolidine (0.26 g, 3.0 mmol) in acetonitrile (20 mL). The solution was treated with potassium carbonate (0.5 g, 3.6 mmol) and heated at 50-55° C. for 20 hours in a sealed flask. The mixture was allowed to cool to room temperature, filtered, and the filtrate was concentrated in vacuo. The residue was diluted with MTBE (20 mL) and water (20 mL) and the pH was adjusted to 3-3.5 with concentrated HCl. The aqueous layer was separated, extracted with MTBE (10 mL), adjusted to a pH of 8-8.5 with potassium carbonate, and extracted with isopropyl acetate (20 mL). The organic layer was separated and concentrated in vacuo. The residue was dissolved in heptane (20 mL), filtered, and the filtrate concentrated under vacuum to provide the title compound. 1H NMR (CDCl3) δ 1.10 (d, J=6.1 Hz, 3H); 1.35-1.49 (m, 1H); 1.62-1.85 (m, 2H); 1.85-1.98 (m, 1H); 2.23 (q, J=8.8. Hz, 1H); 2.28-2.42 (m, 1H); 2.46-2.57 (m, 1H), 3.04-3.19 (m, 2H); 3.19-3.30 (m, 2H); 7.47 (s, 1H); 7.60 (d, J=8.8 Hz, 1H), 7.647.70 (m, 1H), 8.05 (m, 1H); 9.09 (s, 1H); HRMS Calcd. for [C16H19BrN2+H+]: 319.0810. Found: 319.0795.

後処理

  1. temperatureto cool to room temperature
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionThe residue was diluted with MTBE (20 mL) and water (20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with MTBE (10 mL)
  7. extractionextracted with isopropyl acetate (20 mL)
  8. customThe organic layer was separated
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in heptane (20 mL)
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum

出典と根拠

ORDレコード
ord-7d6e6e6ee70f42939f9102d4c833a78f
出典データセット
uspto-grants-2008_11
特許番号
US07456196B2

関連ノート

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