p-Toluenesulfonic acid → 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-4H-1,2,4-triazole

HRID 84521ノート

反応式

HRID 84521 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=O)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:21]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH:28]([NH:30][NH2:31])=O.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]4[N:17]([CH:18]([CH3:20])[CH3:19])[CH:28]=[N:30][N:31]=4)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:21]=1

参加物

8

反応物 5

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 12229HydrazinecarboxaldehydeHCID 24819Phosphorus pentachlorideHCID 579005078-bromo-N-isopropyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

生成物 1

HCID 579003103-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-4H-1,2,4-triazole

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

To a solution of in 8-bromo-N-isopropyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (180 mg, 0.49 mmol) in 5 mL toluene was added phosphorus pentachloride (0.184 g, 0.88 mmol) under nitrogen and the reaction mixture was heated at 80° C. for 2 h. The mixture was cooled and carefully concentrated. The crude residue was dissolved in mL THF and treated sequentially with formyl hydrazine (118 mg, 2.0 mmol) and potassium carbonate (0.340 g, 2.46 mmol). The mixture was stirred overnight at room temperature, diluted with water and extracted with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The crude residue was dissolved in toluene (10 mL) and treated with p-toluenesulfonic acid (15 mg, 0.087 mmol). The whole was sealed and heated at 90° C. for 15 min. The reaction mixture was cooled to room temperature, concentrated, diluted with ethyl acetate and washed with water, sodium bicarbonate and brine. The organics were dried over sodium sulfate and concentrated to give 224 as the crude product which could be used without purification in subsequent operations. A small amount was purified by reverse-phase HPLC for analytical purposes. 1H NMR (dmso-d6, 400 MHz) δ 11.9 8.84 (s, 1H), 7.65 (d, 1H), 7.45 (s, 1H), 7.32-7.27 (m, 2H), 4.75 (m, 1H), 4.34 (t, 2H), 3.25 (t, 2H), 1.48 (d, 6H). MS (ESI) 392.1

後処理

  1. temperatureThe mixture was cooled
  2. concentrationcarefully concentrated
  3. dissolutionThe crude residue was dissolved in mL THF
  4. extractionextracted with ethyl acetate
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. dissolutionThe crude residue was dissolved in toluene (10 mL)
  9. customThe whole was sealed
  10. temperatureheated at 90° C. for 15 min
  11. temperatureThe reaction mixture was cooled to room temperature
  12. concentrationconcentrated
  13. additiondiluted with ethyl acetate
  14. washwashed with water, sodium bicarbonate and brine
  15. dry with materialThe organics were dried over sodium sulfate
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-0421e20749bc42b0aa0fd3b2beaf0007
出典データセット
uspto-grants-2014_09
特許番号
US08846762B2

反応ノート

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