Triethylamine → 3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-7-(3-pyridinyl)isoquinoline

HRID 860881ノート

反応式

HRID 860881 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[C:12]([CH2:17][CH2:18]O)[N:13]=[CH:14]3)=[CH:9][CH:8]=2)[CH:2]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.C([O-])([O-])=O.[K+].[K+].[CH3:38][C@@H:39]1[CH2:43][CH2:42][CH2:41][NH:40]1>C(Cl)Cl.C(#N)C>[CH3:38][C@@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1[CH2:18][CH2:17][C:12]1[N:13]=[CH:14][C:15]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[CH:16]=2

参加物

8

反応物 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 641544(R)-2-MethylpyrrolidineHCID 671043582-[7-(3-Pyridinyl)-3-isoquinolinyl]ethanol

生成物 1

HCID 251970903-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-7-(3-pyridinyl)isoquinoline

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

The product from Example 63A (0.25 g, 1.0 mmol) and triethylamine (0.15 g, 1.5 mmol) in methylene chloride (10 mL) at −5° C. were treated with methanesulfonyl chloride (0.12 g, 1.2 mmol) and stirred at 0° C. for 2 hours and then stirred at room temperature for 15 hours. The mixture was concentrated under reduced pressure and the residue was treated with K2CO3 (0.21 g, 1.5 mmol) and (2R)-2-methylpyrrolidine (0.13 g, 1.5 mmol) in acetonitrile (15 mL), and then heated at 60° C. for 5 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in 30 mL methylene chloride, washed with 10 mL 15% NaCl, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10:90:1 MeOH:CHCl3:Et3N) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.27 (s, 1H), 8.95 (m, 1H), 8.64 (dd, J=2, 4 Hz, 1H), 8.12 (s, 1H), 7.98 (m, 1H), 1.90–1.86 (m, 2H), 7.56 (s, 1H), 7.44–7.40 (m, 1H), 3.37–3.28 (m, 2H), 3.26–3.18 (m, 2H), 2.68–2.61 (m, 2H), 2.51–2.46 (m, 1H), 2.38–2.31 (m, 1H), 2.00–1.93 (m, 1H), 1.88–1.82 (m, 1H), 1.80–1.72 (m, 1H), 1.55–1.46 (m, 1H), 1.14 (d, 3H); 13C NMR (CDCl3, 400 MHz) δ 9.27 153.8, 151.9, 148.4, 147.9, 135.6, 135.5, 135.4, 134.1, 129.1, 127.0, 126.9, 125.2, 123.4, 118.2, 60.4, 54.1, 54.0, 37.2, 32.8, 21.9, 19.0.

後処理

  1. stirringstirred at room temperature for 15 hours
  2. concentrationThe mixture was concentrated under reduced pressure
  3. temperatureheated at 60° C. for 5 hours
  4. concentrationThe mixture was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in 30 mL methylene chloride
  6. washwashed with 10 mL 15% NaCl
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (silica gel, 10:90:1 MeOH:CHCl3:Et3N)

出典と根拠

ORDレコード
ord-9b8b8144cfaf41fc8017fd5df83a987e
出典データセット
uspto-grants-2006_12
特許番号
US07153889B2

反応ノート

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