Toluene → 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazol-5(4H)-one

HRID 84551

반응식

HRID 84551 반응식
[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.C1(C)C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C(Cl)Cl.[NH:38]([C:40](OC)=[O:41])[NH2:39].C(=O)([O-])[O-].[K+].[K+]>C(=O)(O)[O-].[Na+].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])[C:40](=[O:41])[NH:38][N:39]=4)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:21]=1

참가 물질

9

반응물 6

HCID 1140TolueneHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 24819Phosphorus pentachlorideHCID 80519Methyl carbazateHCID 579005078-bromo-N-isopropyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

생성물 1

HCID 579000953-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazol-5(4H)-one수율 36.9%

시약·촉매·용매 2

HCID 962Water용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
80 °C

실험 절차

A solution of 8-bromo-N-isopropyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (200 mg, 0.5 mmol) in toluene (5 mL, 0.05 mol) under nitrogen atmosphere was treated with phosphorus pentachloride (0.182 g, 0.87 mmol) in one portion. The flask was sealed and heated at 80° C. for 2 h, cooled to room temperature and the solvent concentrated under reduced pressure with care to avoid atmospheric exposure. The crude residue was taken up in methylene chloride (8 mL, 0.1 mol) and treated with methyl hydrazinecarboxylate (0.123 g, 1.36 mmol). The resulting suspension was stirred at room temperature for 2 h. The reaction mixture was diluted with saturated sodium bicarbonate and extracted with methylene chloride. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The crude residue was dissolved in ethanol (5 mL) and potassium carbonate (0.2264 g, 1.64 mmol) was added. The reaction mixture was stirred at 80° C. for 2 h. 0.5 mL water was added and the heating continued overnight. The mixture was concentrated, diluted with water and extracted with ethyl acetate. The organics were washed with brine, concentrated, and the resultant residue purified by flash column chromatography to give 265 (75 mg). 1H NMR (dmso-d6, 500 MHz) δ 11.9 (s, 1H), 7.60 (m, 1H), 7.30-7.23 (m, 3H), 4.44 (pentet, 1H), 4.32 (t, 2H), 3.22 (t, 2H), 1.46 (d, 6H). MS (ESI) 408.1

후처리

  1. customThe flask was sealed
  2. temperaturecooled to room temperature
  3. concentrationthe solvent concentrated under reduced pressure with care
  4. extractionextracted with methylene chloride
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. dissolutionThe crude residue was dissolved in ethanol (5 mL)
  9. stirringThe reaction mixture was stirred at 80° C. for 2 h
  10. waitthe heating continued overnight
  11. concentrationThe mixture was concentrated
  12. additiondiluted with water
  13. extractionextracted with ethyl acetate
  14. washThe organics were washed with brine
  15. concentrationconcentrated
  16. customthe resultant residue purified by flash column chromatography

출처 및 근거

ORD 기록
ord-72b0676c6fa742d6a880991ea19db55a
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846762B2

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