2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde → (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazol-3-yl]-methanol

HRID 1952168노트

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HRID 1952168 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[CH2:27]([N:29]1[C:33]([CH:34]=[O:35])=[CH:32][C:31]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)=[N:30]1)[CH3:28]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:34]([C:33]3[N:29]([CH2:27][CH3:28])[N:30]=[C:31]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=4)[CH:32]=3)[OH:35])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

참가 물질

5

반응물 3

HCID 576192072-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehydeHCID 580879285-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, 화합물

생성물 1

HCID 57619398(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazol-3-yl]-methanol수율 55.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-20 °C

실험 절차

5-Chloro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (629, 0.15 g, 0.34 mmol) was dissolved in tetrahydrofuran (3 mL, 40 mmol) and the solution was cooled to −20° C. 2 M isopropylmagnesium chloride in tetrahydrofuran (200 μL) was added dropwise and the reaction was stirred and allowed to warm to −5° C. After the reaction was cooled to −20° C., 2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde (530, 0.043 g, 0.17 mmol, prepared as described in Example 47, Scheme 162, Step 5) in tetrahydrofuran (4 mL) was added to the mixture. The reaction was stirred to −5° C., then concentrated, ethyl acetate was added and the mixture was washed with sodium bicarbonate saturated solution and brine. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Purification with silica gel column chromatography eluting with a gradient of ethyl acetate (5-80%) in hexanes gave the desired compound (630, 0.038 g, 40%).

후처리

  1. temperatureto warm to −5° C
  2. temperatureAfter the reaction was cooled to −20° C.
  3. stirringThe reaction was stirred to −5° C.
  4. concentrationconcentrated
  5. additionethyl acetate was added
  6. washthe mixture was washed with sodium bicarbonate saturated solution and brine
  7. dry with materialAfter drying over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customPurification with silica gel column chromatography
  10. washeluting with a gradient of ethyl acetate (5-80%) in hexanes

출처 및 근거

ORD 기록
ord-782acb4a2db94c52ac8587ff5c024b07
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08404700B2

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