Potassium Iodide → 1'-{[5-(Benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3'-indol]-2'(1'h)-one

HRID 1965668ノート

反応式

HRID 1965668 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3[C:14]4[C:18]([CH:19]=[CH:20][C:12]=3[O:11][CH2:10]2)=[N:17][O:16][N:15]=4)[C:2]1=[O:21].[H-].[Na+].[CH2:24]([O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38]Cl)=[N:36][CH:37]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[I-].[K+].[Cl-].[NH4+]>CN(C)C=O.O>[CH2:24]([O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4[C:14]5=[N:15][O:16][N:17]=[C:18]5[CH:19]=[CH:20][C:12]=4[O:11][CH2:10]3)[C:2]2=[O:21])=[N:36][CH:37]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

参加物

8

反応物 5

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178541585-(Benzyloxy)-2-(chloromethyl)pyridineHCID 593526377H-spiro[benzofuro[4,5-c][1,2,5]oxadiazole-8,3'-indolin]-2'-one

生成物 1

HCID 593522131'-{[5-(Benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3'-indol]-2'(1'h)-one収率 5.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 7H-spiro[benzofuro[4,5-c][1,2,5]oxadiazole-8,3′-indolin]-2′-one (0.400 g, 1.4 mmol) in anhydrous N,N-dimethylformamide (7 mL) was added sodium hydride (60% w/w dispersion in mineral oil, 0.086 g, 3.6 mmol) at 0° C. and the mixture was stirred for 20 minutes. 5-(Benzyloxy)-2-(chloromethyl)pyridine (0.44 g, 1.9 mmol) was added and the reaction mixture was stirred at ambient temperature for 19 h. Potassium iodide (˜10 mg, catalytic amount) was added and the reaction mixture was stirred at 60° C. for 2 h, at ambient temperature for 43 h, at 60° C. for 7 h and at ambient temperature for 3 days. Saturated aqueous ammonium chloride (7 mL) and water (30 mL) were added and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with water (2×20 mL) and brine (20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with hexanes/ethyl acetate (3/2), followed by trituration in hexanes to afford 1′-{[5-(benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3′-indol]-2′(1′H)-one (0.034 g, 5%) as a pale yellow solid: mp 209-212° C.; 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J=2.7 Hz, 1H), 7.83 (d, J=9.6 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.45-7.23 (m, 8H), 7.18 (d, J=7.5 Hz, 1H), 7.03 (t, J=7.5 Hz, 1H), 6.92 (J=7.8 Hz, 1H), 5.39 (d, J=15.9 Hz, 1H), 5.27 (d, J=9.6 Hz, 1H), 5.11 (s, 2H), 4.99 (d, J=9.3 Hz, 1H), 4.87 (d, J=15.9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ176.0, 163.0, 154.4, 148.3, 147.1, 144.9, 142.2, 137.8, 136.0, 129.8, 129.7, 128.7, 128.3, 127.6, 123.7, 123.6, 122.4, 122.3, 121.9, 119.3, 110.2, 107.0, 82.0, 70.4, 57.4, 46.0; MS (ES+) m/z 477.2 (M+1).

後処理

  1. stirringthe reaction mixture was stirred at ambient temperature for 19 h
  2. stirringthe reaction mixture was stirred at 60° C. for 2 h, at ambient temperature for 43 h, at 60° C. for 7 h and at ambient temperature for 3 days
  3. extractionthe mixture was extracted with ethyl acetate (3×10 mL)
  4. washThe combined organic extracts were washed with water (2×20 mL) and brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with hexanes/ethyl acetate (3/2)

出典と根拠

ORDレコード
ord-4b598e22791847bfbba1a41df80444ca
出典データセット
uspto-grants-2013_04
特許番号
US08415370B2

反応ノート

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