p-Toluenesulfonic acid → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid

HRID 2367697노트

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HRID 2367697 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([OH:13])=[O:12].[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19][O:14]1)[N:6]=[C:5]2[C:11]([OH:13])=[O:12]

참가 물질

5

반응물 3

HCID 6101p-Toluenesulfonic acid2회HCID 80803,4-dihydro-2H-pyran2회HCID 71573585-bromo-1H-indazole-3-carboxylic Acid

생성물 1

HCID 698056555-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid수율 60.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

To a solution of 5-bromo-1H-indazole-3-carboxylic acid (CXV) (59.8 g, 248 mmol) in THF (800 mL) under argon was added 3,4 dihydro-2H-pyran (50.6 mL, 558 mmol) and p-TsOH (4.72 g, 24.8 mmol). The reaction was heated to reflux at 60° C. for 16 h. An additional portion of p-TsOH (0.025 eq) and 3,4 dihydro-2H-pyran (0.56 eq) was added and the reflux continued for 5 h. The solution was concentrated under vacuum. EtOAc was added to the residue and the suspension was filtered and dried under high vacuum overnight to produce 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (CXVIII) as a white solid (49.07 g, 150.9 mmol, 60.8% yield). ESIMS found for C13H13BrN2O3 m/z 326.3 (M+H).

후처리

  1. temperatureThe reaction was heated
  2. concentrationThe solution was concentrated under vacuum
  3. additionEtOAc was added to the residue
  4. filtrationthe suspension was filtered
  5. customdried under high vacuum overnight

출처 및 근거

ORD 기록
ord-4dd9615f77334af897f54dd3fd46a5da
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697887B2

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